ABPA and aspergillus lung infection, cystic fibrosis patients RHC

Objectives

Guidance for clinicians and healthcare staff on the diagnosis and treatment of Allergic bronchopulmonary aspergillosis

Scope

Patients under the care of the paediatric cystic fibrosis unit RHC Glasgow

Audience

CF Team, medical staff covering general wards, pharmacists

Allergic bronchopulmonary aspergillosis (ABPA) and aspergillus lung infection in paediatric cystic fibrosis patients – diagnosis and management RHC CF Unit Glasgow

ABPA

Allergic bronchopulmonary aspergillosis (ABPA) is seen in approximately 10% of patients with cystic fibrosis (CF) and can be difficult to diagnose. Diagnostic criteria require an evaluation of clinical and radiological signs, lung function trend and serum immunologic markers such as total Ig E , Aspergillus IgE and Aspergillus IgG.

DIAGNOSIS

Bloods – 2 or more are suggestive of ABPA

Total IgE > 450 KU/L
Specific IgE > 0.35 KU/L
Specific IgG > 90 mA/L
Eosinophils > 0.4

Sputum / Cough Swabs

Aspergillus fumigatus may or may not be present in respiratory cultures.

TREATMENT

Treatment of ABPA includes a combination of oral Prednisolone plus an oral anti-fungal agent.

PREDNISOLONE

VORICONAZOLE

Due to difficulties with obtaining adequate drug levels with Itraconazole, Voriconazole is used as

1^st line anti-fungal therapy. Long-term Voriconazole use has been associated with a rasied risk of skin cancer and so maximum duration of treatment is 3/12 then change to Posaconazole ( see Table for dosing ) if continuing ABPA treatment.

ORAL

VORICONAZOLE

2-12 years

9mg/kg twice a day (max

350mg twice a day)

12-15 years

Body weight under

50kg

9mg/kg twice a day (max

350mg twice a day)

Body weight over 50kg

Dose as for child 1518years and body weight over 40kg

15-18 years

Body weight under

40kg

200mg twice a day for 2 doses then 100mg twice a day (may be increased to 150mg)

Body weight over 40kg

400mg twice a day for 2 doses then 200mg twice a day (may be increased to 300mg)

Take an hour before food or 2 hours after food

Suspension has 14 day expiry once reconstituted

Monitor U&E’s, LFT’s

Drug levels – trough level pre dose after

3 days. Aim for voriconazole level 1 - 6mg/L

Consult pharmacist if result out of range.

Adverse effects; Photosensitivity (prescribe sunscreen) GI upset, visual disturbance (colour and perceptual changes), liver abnormalities, cardiac effects (tachy/bradycardia, hypotension, arrhythmias,

QT prolongation.

Always check interactions; care with

other drugs that prolong the QT interval – ECG

Interacts with Ivacaftor –reduce Ivacaftor dose to 1xdose twice a week.

MAX 3/12 – then change to Posaconazole if continuing ABPA treatment

Monitor ABPA Serology, FEV1 and symptoms

POSACONAZOLE

ORAL

POSACONAZOLE

Oral suspension

< 8 years

10-12mg/kg/day in two doses . May require up to

18mg/kg /day

>8 years:

400mg BD

Monitor levels. Monitor liver function tests monthly.

The tablet and oral suspension are not to be used interchangeably due to the differences in the dosing of each formulation.

Tablets should be used preferentially as more consistent levels may be obtained.

Suspension should be taken immediately following a meal (preferably fatty meal) to enhance absorption. If this is not possible, may need to use 200mg QDS dosing. Tablets can be taken with or without a meal.

Adverse effects; Photosensitivity (prescribe sunscreen) GI upset, visual disturbance (colour

and perceptual changes), liver abnormalities, cardiac effects (tachy/bradycardia, hypotension, arrhythmias)

Levels should be monitored on initiation, on amendment of dosage, if an interacting drug is commenced or efficacy is not observed.

Pre-dose samples (if not possible then a random sample) taken after at least 1 week on therapy.

Aim: 1 - 5mg/L For levels >5mg/L review dose with consultant and pharmacist.

Note interaction with Rifampicin. Levels when using suspension reduced by Ranitidine and proton pump inhibitors which should be stopped if possible.

Interacts with Ivacaftor –

reduce Ivacaftor dose to 1x dose twice a week

QT prolongation.

Always check interactions; care with other drugs that prolong the QT interval – ECG

Monitor U+E ; LFTs @ 2 weeks then monthly

Oral tablets

>8 years:

300mg BD on day 1,

then 300mg OD thereafter Monitor levels. Monitor liver function tests monthly

Aspergillus lung infection

DIAGNOSIS

This is a relatively rare complication in CF. Diagnosis may be suspected if some of the following criteria are met:

Aspergillus in sputum
Worsening CXR infiltrates +/- cavitation and nodules
Unresponsive to standard IV antibiotic treatment
Elevated serum Galactomannan ( Asp.fumigatus cell wall component)
+/- Elevated Aspergillus fumigates IgE/ IgG

TREATMENT

If pulmonary infection is believed to be due to Aspergillus a 2 week course of IV Voriconazole followed by oral Voriconazole may be considered.

DRUG

DOSE

NOTES

VORICONAZOLE

2 WEEK COURSE

2-12 years

9mg/kg every 12 hours for 24hours then 8mg/kg every 12 hours thereafter

12 to 14 years and <50 kg

9mg/kg every 12 hours for 24hours then

8mg/kg every 12 hours thereafter

12 to 14 years and >50 kg and 15 to 17 years regardless of body weight

6mg/kg every 12 hours for 2 doses then

4mg/kg every 12 hours

(reduce to 3mg/kg if not tolerated)

CHANGE TO ORAL VORICONAZOLE AT END OF IV COURSE.

CONSIDER ORAL POSACONAZOLE IF ADEQUATE VORICONAZOLE

LEVELS CANNOT BE OBTAINED.

( SEE TABLE ABOVE FOR ORAL VORICONAZOLE / POSACONAZOLE DOSING) .

Give by intravenous infusion at a rate not exceeding 3mg/kg/hour. Monitor U&E’s, LFT’s weekly

Drug levels – trough level pre dose after 3 days. Aim for voriconazole level 1 - 6mg/L Consult pharmacist if result out of range

Adverse effects/interactions; Photosensitivity (prescribe sunscreen) GI upset, visual disturbance (colour

and perceptual changes), liver abnormalities, cardiac effects (tachy/bradycardia, hypotension, arrhythmias,QT prolongation. - care with other drugs that

prolong the QT interval - ECG

IVACAFTOR.reduce Ivacaftor

dose to 1xdose twice a week

MAX DURATION OF

VORICONAZOLE TREATMENT

IS 3 MONTHS THEN CHANGE

TO POSACONAZOLE

References

Serologic diagnosis of allergic bronchopulmonary aspergillosis in patients with cystic fibrosis through the detection of immunoglobulin G to Aspergillus fumigatus R.C. Barton et al. / Diagnostic Microbiology and Infectious Disease 62 (2008) 287–291

Aspergillus bronchitis in cystic fibrosis Shoseyov D, Brownlee KG, Conway SP, Kerem E. Chest 2006;130:222–6.

Clinical Guidelines:Care of Children with Cystic Fibrosis Royal Brompton Hospital 2014/5

CF Trust “ Antibiotic Treatment for Cystic Fibrosis ” 2009 Section 7.9 ABPA