Download TOBI® (nebulised tobramycin)

Gwent Shared Care Protocol
TOBRAMYCIN nebuliser solution
300mg/5mL (TOBI®) or 300mg/4mL (Bramitob®)
for the treatment of Cystic Fybrosis
Protocol No. 16
General guidance
PLEASE CHECK http://www.gpmtc.wales.nhs.uk
FOR THE LATEST VERSION OF THIS PROTOCOL
The Gwent Partnership Medicines and Therapeutics Committee have endorsed this protocol.
They outline the shared care arrangements for patients using nebulised tobramycin and
should be read in conjunction with the
1. Shared Care Agreement Form (see below)
2. The appropriate Summary of Product Characteristics (SmPC)
Tobi® SmPC: http://www.medicines.org.uk/emc/medicine/19020/SPC/
Bramitob® SmPC:
http://www.medicines.org.uk/emc/medicine/21427/SPC/
1. Licensed Indications
Long-term management of chronic pulmonary infection due to Pseudomonas aeruginosa in
cystic fibrosis (CF) patients aged 6 years and older.
Consideration should be given to official guidance on the appropriate use of antibacterial
agents
2. Therapeutic use &
background
The choice of antibiotics for cystic fibrosis is based on the susceptibility patterns of the
micro-organism and the patient’s ability to tolerate different drugs. In the UK only two
antibiotics are licensed for administration by nebulisation; colistin and tobramycin.
Tobramycin is considered suitable for patients chronically colonised with Pseudomonas
aeruginosa and whose lung function (FEV1) continues to decline or excessively declines
(measured as greater than or equal to 4% per year) despite compliance with the standard
current practice of nebulised colistin (2MU) or if colistin is not tolerated. Cystic Fibrosis
Centre Cardiff state that these patients would also be expected to have had 4
exacerbations requiring IV antibiotics in 1 year.
The 2003 Cochrane Collaboration review1 of nebulised anti-pseudomonal antibiotics for CF
concluded that, “Nebulised anti-pseudomonal antibiotic treatment improves lung function.
However, more evidence, from longer duration trials, is needed to determine if this benefit
is maintained as well as to determine the significance of development of antibiotic resistant
organisms.”
Safety and efficacy have been assessed in controlled and open label studies for up to 96
weeks (12 cycles), but have not been studied in patients < 6 years of age, patients with
FEV1 <25% or>75% predicted, or patients colonised with Burkholderia cepacia.
3. Contraindications &
Cautions
Patients with known hypersensitivity to any aminoglycoside.
Other cautions:
 known or suspected renal, auditory, vestibular or neuromuscular dysfunction, or with
severe, active haemoptysis.
 Patients receiving potent diuretics, such as furosemide.
Pregnancy: Nebulised tobramycin should not be used unless the benefits to the mother
outweigh the risks to the foetus or baby.
Breast-feeding: Because of the potential for ototoxicity and nephrotoxicity with
tobramycin in infants, a decision should be made whether to terminate nursing or
discontinue Tobi therapy.
1
Ryan G, Mukhopadhyay S, Singh M. Nebulised anti-pseudomonal antibiotics for cystic fibrosis. Cochrane Database of Systematic
Reviews 2003, Issue 3. Art. No.: CD001021. DOI: 10.1002/14651858.CD001021.
http://www.mrw.interscience.wiley.com/cochrane/clsysrev/articles/CD001021/frame.html
This Shared Care Protocol should be read in conjunction with the Summary of Product Characteristics
Status: APPROVED
Issue Date: May 2007 (Revised Feb 2012)
Approved by: GPMTC
Page 1 of 5
Review Date: Feb 2015
4. Typical dosage
regimen (adults)
The recommended dose for adults and children is one ampoule (300mg) nebulised twice
daily for 28 days. Dosage is not adjusted for weight.
The dose interval should be as close as possible to 12 hours and not < 6 hours.
After 28 days of therapy, patients should stop nebulised tobramycin therapy for the next
28 days.
A cycle of 28 days of active therapy and 28 days of rest from treatment should be
maintained. The specialist may recommend use of colistin during the ‘rest’ month.
Nebulised tobramycin is inhaled whilst the patient is sitting or standing upright and
breathing normally through the mouthpiece of the nebuliser. Nose clips may help the
patient breathe through the mouth. The patient should continue their standard regimen of
chest physiotherapy. The use of appropriate bronchodilators should continue as thought
clinically necessary. Where patients are receiving several different respiratory therapies it
is recommended that they are taken in the following order: bronchodilator, chest
physiotherapy, other inhaled medicinal products, and finally nebulised tobramycin.
All dose adjustments will be undertaken by specialist unless directions have been specified
in the medical letter to the GP.
5. Drug interactions
For a comprehensive
list consult the BNF
(Appendix
I)
or
Summary of Product
Characteristics.
Concurrent and/or sequential use with other drugs with nephrotoxic or ototoxic potential
should be avoided. Some diuretics can enhance aminoglycoside toxicity.
Nebulised tobramycin should not be administered concomitantly with furosemide, urea or
mannitol.
No interactions have been noted when nebulised tobramycin was taken concomitantly
with dornase alfa (Pulmozyme®), inhaled corticosteroids, beta agonists, and other oral or
parenteral antipseudomonal antibiotics.
6. Adverse drug
reactions
Although nephrotoxicity has been associated with parenteral aminoglycoside therapy,
there was no evidence of nephrotoxicity during clinical trials with Tobi®.
Any serious reaction to
an established drug
should be reported to
CHM.
Occurrence
- reported frequency
Adverse effect
Respiratory system
- uncommon
Voice alteration (including hoarseness), dyspnoea,
increased cough, pharyngitis.
Respiratory system
- rare
Bronchospasm, chest tightness, cough, shortness of
breath, lung disorder, increased sputum, asthma
haemoptysis, decreased lung function, laryngitis,
Epistaxis, rhinitis
Ear disorder, ear pain.
Tinnitus, taste perversion, hearing loss, aphonia.
ENT rare
- very rare
Special senses
- rare
Skin -rare
Respiratory system
- uncommon
Action
Seek
specialist
advice
Rash.
Voice alteration (including hoarseness), dyspnoea,
increased cough, pharyngitis.
For a comprehensive list, or if significance of possible adverse event uncertain, consult
product literature, BNF or contact specialist.
The patient should be advised to report any of the following signs or symptoms without
delay: Tinnitus or hearing loss.
7. Baseline
investigations
To be undertaken by specialist centre:
Rate of decline of FEV1 (% predicted) over last 6-12 months.
FEV1, sputum culture and sensitivities, renal function, weight.
Pure tone audiometry may be considered in patients with a predisposing risk.
This Shared Care Protocol should be read in conjunction with the Summary of Product Characteristics
Status: APPROVED
Issue Date: May 2007 (Revised Feb 2012)
Approved by: GPMTC
Page 2 of 5
Review Date: Feb 2015
8. Monitoring
TO BE UNDERTAKEN BY SPECIALIST CENTRE
Specialist reviews typically include documentation of physiotherapy regime, general wellbeing score and CF symptom score.
At 1month after starting treatment
FEV1 , sputum culture/sensitivities and renal function
At 3 months after starting treatment
FEV1 , sputum culture/sensitivities
At 6 months
Patients will continue treatment provided that there is an improvement of FEV1
after the first month of treatment of over 7% OR the rate of decline of FEV1 over
the first 6 months is improved, and the patient is compliant with treatment.
At 12 months
Patients will continue treatment provided that the rate of decline of FEV1 is
consistently improved and/or there is a reduction in IV antibiotic use and the
patient is compliant and there is an improvement in weight gain and well-being.
Monitoring parameters &
Frequency
Laboratory results
& responsibility
Action to be taken if abnormal result identified by GP
U&E/Cr after every 6
completed cycles –
Once yearly
Creatinine >100
mol/l
Stop drug and discuss. If there is evidence of
nephrotoxicity, all tobramycin therapy should be
discontinued until trough tobramycin serum
levels fall below 2g/ml. Seek specialist’s advice
before reintroducing treatment.
Stop drug and discuss.
By specialist
Audiology
only if patient reports
tinnitus or hearing loss
By primary care or
specialist
9. Pharmaceutical
aspects
Both Tobi® and Bramitob® ampoules should be stored in a refrigerator at 2 to 8°C.
Intact ampoules (in foil bags) may be stored at up to 25°C for up to 28 days.
The nebuliser solution is ready to use, doesn’t froth and is preservative free. The contents
of one ampoule should be emptied into the nebuliser and administered by inhalation over
approximately a 15-minute period using a hand-held PARI LC PLUS reusable nebuliser with
a suitable compressor.
Suitable compressors are those which, when attached to a PARI LC Plus nebuliser, deliver a
flow rate of 4 to 6 L/min and/or a back pressure of 110-217 kPa (
An e-flow nebuliser may also be used.
10. Specialist centre
contact information
If stopping medication or needing advice please contact:
Dr Marcus Pierrepoint or Dr Ian Bowler
Dept of Child Health, Royal Gwent Hospital, Newport. Tel. No. 01633 234613
For adult patients under the care of the Cystic Fibrosis Centre in Cardiff (Llandough
Hospital) contact:
Dr Ian Ketchell 02920 715382
Or Physiotherapists 02920 711711 bleep 989 (08.30am to 16.30pm Mon to Fri).
CF Pharmacist 02920715261
11. Criteria for shared
care
12. Responsibilities of
specialist centre
Prescribing responsibility will only be transferred when
 Treatment is for a specified indication and duration.
 Treatment has been initiated and established by the cystic fibrosis specialist.
 The patient’s initial reaction to and progress on the drug is satisfactory.
 The GP has agreed in writing in each individual case that shared care is appropriate.
 The patient’s general physical, mental and social circumstances are such that he/she
would benefit from shared care arrangements.
1. Determine when initiation of treatment with Tobi®/Bramitob® is appropriate.
2. Supervise the initial dose of Tobi®/Bramitob® (risk of bronchospasm) and monitor
response to treatment as above.
This Shared Care Protocol should be read in conjunction with the Summary of Product Characteristics
Status: APPROVED
Issue Date: May 2007 (Revised Feb 2012)
Approved by: GPMTC
Page 3 of 5
Review Date: Feb 2015
3. Undertake monitoring.
4. Ensure that the patient has an adequate supply of medication (usually 28 days) until
shared care arrangements are in place.
5. Respond to GP request to review the patient due to adverse effects of therapy.
Provide GP with:
1. Initiation letter (which includes diagnosis, relevant clinical information and baseline
results, treatment to date and treatment plan, duration of treatment before consultant
review).
2. Details of outpatient consultations, ideally within 14 days of seeing the patient,
including electrolyte result when taken and presence/absence of auditory symptoms.
3. Advice on when to stop Tobi®/Bramitob® therapy.
4. Inform GP if patient does not attend outpatient appointment
Provide patient/carer with:
1. Suitable nebuliser / compressor.
2. Information on the potential benefits and side effects of treatment.
3. Details of the necessary monitoring, storage and administration requirements for
Tobi® or Bramitob®.
13. Responsibilities of
primary care
1. To prescribe according to this protocol.
2. Symptoms or results are appropriately actioned, recorded and communicated to
specialist centre when necessary.
3. Report to, and seek advice from, the specialist on any aspect of patient care which is
of concern or may affect treatment (including potential non-compliance).
4. Stop treatment on advice of the specialist
14. Responsibilities of
patients/carers
1. Ensure they have a clear understanding of their treatment including how to store and
administer the nebuliser solution.
2. To attend hospital and GP clinic appointments, failure to attend will result in medication
being stopped.
3. To report adverse effects to their specialist or GP.
15. Additional
responsibilities
Any suspected serious adverse reaction to an established drug should be reported to
MHRA via the “yellow card scheme.” http://yellowcard.mhra.gov.uk/
16. Supporting
documentation
Patient information leaflets:
Tobi®:
http://www.medicines.org.uk/EMC/medicine/19616/PIL/TOBI+300+mg+5+ml+Nebuliser+S
olution/
Bramitob®:
http://www.medicines.org.uk/EMC/medicine/21475/XPIL/Bramitob+Nebuliser+Solution/
All Wales Shared Care Template for tobramycin at:
http://www.wales.nhs.uk/sites3/page.cfm?orgid=371&pid=17300
This Shared Care Protocol should be read in conjunction with the Summary of Product Characteristics
Status: APPROVED
Issue Date: May 2007 (Revised Feb 2012)
Approved by: GPMTC
Page 4 of 5
Review Date: Feb 2015
Shared Care Agreement Form - CONFIDENTIAL
CONSULTANT REQUEST
To: Dr.
Your patient:
NHS No. (10digit):
was seen on:
with a diagnosis of:
I recommend that the following drug is initiated:
This drug has been accepted as suitable for shared care by the ABHBMTC. I agree to the responsibilities set out in
the protocol SCP No.
(copy attached). This should be read in conjunction with the definition of shared care at
http://www.wales.nhs.uk/sites3/Documents/371/Doc%202%20Defining%20shared%20care.pdf
I am requesting your agreement to sharing the care of this patient. The preliminary tests set out in the protocol have
been carried out. I am currently prescribing the stabilising treatment.
I would like you to undertake treatment from:
The initial treatment will be:
The baseline tests are:
If you undertake treatment I will reassess the patient in ____ weeks. You will be sent a written summary within 14
days. I will accept referral for reassessment at your request.
The medical staff of the department are available at all times to give you advice.
Consultant Name:
Signature:
Department:
Hospital:
Date:
Contact Telephone Nos:
GP RESPONSE (Please circle the appropriate number below detailing your response)
1. I am willing to undertake shared care as set out in SCP No. _____ for this patient.
2. I would like further information. Please contact me on: _______________________
3. I am unable to undertake shared care for this patient because: (Please state)
_________________________________________________________________________________
G.P. Signature _________________________________________
Date _________
Practice Address/Stamp ________________________________________________
PLEASE RETURN WHOLE COMPLETED FORM OR TO THE REQUESTING CONSULTANT WITHIN 1 WEEK
This Shared Care Protocol should be read in conjunction with the Summary of Product Characteristics
Status: APPROVED
Issue Date: May 2007 (Revised Feb 2012)
Approved by: GPMTC
Page 5 of 5
Review Date: Feb 2015