On behalf of the
GREATER MANCHESTER MEDICINES MANAGEMENT GROUP /
SHARED CARE GUIDELINE for Dornase Alfa (Pulmozyme®) / Reference Number
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Scope: Dornase Alfa for Adult Patients with Cystic Fibrosis / Classification
SHARED CARE GUIDELINE
Issue date : / Replaces: No previous version available
Author(s)/Originator(s) / University Hospital of South Manchester
To be read in conjunction with the following documents / Pharmaceutical company’s patient information leaflet (PIL)
Summary of product characteristics (SPC)
Authorised by / Interface Prescribing Group / Date: March ‘09
Review Date / March 2011
1. Introduction
Cystic fibrosis is an inherited condition which affects chloride transport across the cell membrane. Patients with cystic fibrosis commonly have viscid secretions with high levels of DNA in the lung mucus. This results in recurrent respiratory infections and a vigorous inflammatory process further increasing sputum viscosity making this harder to expectorate. A progressive decline in respiratory status ensues. Recombinant human dornase alfa (DNAse) is a genetically engineered version of a naturally occurring enzyme which cleaves extracellular DNA chains in purulent sputum, thus reducing its viscosity and aiding expectoration and airway clearance. It has been shown to be beneficial in controlled clinical trials. Continuing physiotherapy and antibiotic treatment is required in conjunction with dornase alfa although a reduction in antibiotic use may be seen, as well as improvements in lung function and respiratory symptoms, and avoidance of hospital admission. In severe lung disease, there is evidence that dornase alfa prevents further deterioration or slows it significantly.
The guidance in this protocol should be used in conjunction with the published information about dornase alfa.
2. Scope of treatment: Adults patients with Cystic Fibrosis
As outlined in the NHS Circular 1992 (Gen 11), a consultant may seek the GP’s involvement in prescribing for a patient where there is a shared care agreement. Due to the nature of the management of patients with cystic fibrosis it is generally agreed that a system of shared care with shared commitment between the hospital and GP is desirable. This leaflet provides information on nebulised dornase alfa treatment guidelines for the shared care of therapy between the hospital consultant and GP concerned.
3. Clinical condition being treated
These guidelines will look at the shared care management of patients with cystic fibrosis with dornase alfa. Dornase alfa aids the clearance of sputum in patients with cystic fibrosis by breaking down DNA chains, thus reducing the viscosity of sputum, facilitating expectoration and aiding airway clearance.
Pulmozyme® (dornase alfa) is licensed for the management of cystic fibrosis patients with a forced vital capacity (FVC) of greater than 40% of predicted and over 5 years of age to improve pulmonary function.It may be considered in patients with two or more of the following features:
- Chronic cough (daily) with or without sputum production
- Pseudomonas aeruginosa persistently present in sputum or cough swab
- Best FEV1 < 70% of predicted value
- Patients who require IV antibiotic courses
- Patients awaiting (heart-)lung transplantation
Previous good compliance with treatments is an important requisite.
Monitoring Requirements
None above those that are required for all cystic fibrosis patients, including review of weight, height and respiratory function, as well as clinical assessment in the cystic fibrosis clinic every 2 months.
4. Product information and treatment regimen to be used
Dose & Route of administration
Dornase alfa nebuliser solution is presented as single use ampoules containing 2.5mg (2,500 IU) dornase alfa in 2.5ml of nebuliser solution (brand name: Pulmozyme®).
The undiluted contents of one ampoule (2.5mg) should be administered by inhalation once daily using a recommended jet nebuliser and compressor system at least 1 hour before physiotherapy. Some patients may benefit from twice daily dosage.
A test dose should be administered at the Manchester Adult Cystic Fibrosis Centre and lung function monitored before and after treatment. This first dose should be given under supervision in case of bronchospasm.
Training on the use of the nebuliser (supplied and maintained by the Cystic Fibrosis Centre), as well as correct storage and administration of treatment, will take place at the Manchester Adult Cystic Fibrosis Centre.
Duration of treatment
The first month of treatment will be prescribed by the Manchester Adult CF centre and benefits of treatment assessed. In those patients that have demonstrated a positive response to this initial treatment period GPs will be asked to continue to prescribe dornase alfa.
Where the benefits of treatment are unclear at 1 month the trial period will be extended for up to 6 months with regular assessment at the Manchester Adult CF Centre. In these patients the GP will be asked to prescribe dornase alfa after the first month’s treatment. Treatment will be stopped at 6 months in patients where there has been no benefit gained.
All patients who appear to derive benefit should continue daily treatment for 1 year, when continuing need should be reviewed. When no benefit is seen, treatment is to be discontinued (by the consultant). Subsequent review may indicate that such patients might merit a further trial of treatment at a later time.
Dornase alfa therapy can be safely continued in patients who experience exacerbation of respiratory tract infection. Standard regimens of chest physiotherapy and regular medical care should continue during dornase alfa therapy.
5. Regimen Management
a) Aspects of care for which the Consultant is responsible
· Assess the patient and establish the need and suitability for dornase alfa treatment (according to agreed criteria).
· Initiate treatment with a test dose.
· The patient will be continued to be reviewed in by the Consultant in the context of the routine review of cystic fibrosis 6 times per year in the clinic, along with respiratory function tests and monitoring the patient’s height and weight.
· Provide information and training for patients and their carers.
· A patient information leaflet, provided by the manufacturing company will be supplied to the patient. Training on the use of the nebuliser, as well as correct storage and administration of treatment, will take place at the Cystic Fibrosis Centre. The Cystic Fibrosis Centre will take responsibility for any problems with the nebuliser technology.
· Discuss with the patient (and his/her carers) the benefits and side effects of treatment.
· Send a letter to the GP inviting shared care for the patient.
· The hospital will provide supplies of dornase alfa the first four weeks of treatment until shared care is agreed with the GP.
· Continuing clinical assessment of the patient to ensure ongoing appropriateness of treatment and prompt communication with the GP of any changes of therapy.
· To keep the GP informed of the patient’s progress whilst on therapy.
b) Conditions of assuming responsibility by the GP
The patient has been stabilised on treatment and the GP has agreed to shared care.
c) Aspects of care for which the GP is responsible
· The GP will notify the Consultant if willing to accept shared care after the patient has been stabilised.
· The GP will be responsible for the ongoing prescribing of dornase alfa (in boxes of 30), in the context of prescribing the overall continuing medication for the patient with cystic fibrosis and in the context of wider GP involvement in the continuing care of the patient.
· The GP will liaise with the Cystic Fibrosis Centre if problems arise, including any side effects reported by the patient, in order to decide the preferred course of action.
· The GP will be responsible for promoting compliance.
Information to be supplied to the GP
The Summary of Product Characteristics and a copy of the Shared Care Protocol.
6. Summary of cautions, contra indications, side-effects
NB This will not replace the SPC and should be read in conjunction with it
Possible adverse effects of treatment
Adverse reactions attributed to dornase alfa are rare (<1/1000), in most cases are mild and transient in nature and do not require alterations in dosing. These adverse reactions include chest pain (pleuritic/non-cardiac), fever, dyspepsia, pharyngitis, voice changes, laryngitis, conjunctivitis, dyspnoea, rhinitis, decreased lung function (transient), increased sputum production, rashes and urticaria have been reported.
The development of dornase alfa antibodies occurs in <5% of patients treated. The clinical significance is unknown but it does not affect the improvement in lung function.
If the patient should suffer from any side effects, then these should be reported to the Cystic Fibrosis Centre where the preferred course of action will be decided.
Contra-indications
Patients with a known hypersensitivity to dornase alfa or the excipients of the product.
Pregnancy and lactation
The safety of dornase alfa has not been established in pregnant women, therefore caution should be exercised when prescribing to pregnant women. Animal studies have shown no evidence of impaired fertility, teratogenicity or developmental defects. Advising patients/carers is the responsibility of the Respiratory Consultant.
As it is not known whether dornase alfa is excreted in breast milk, caution should be exercised when dornase alfa is administered to a breast-feeding woman. When administered according to the dosage recommendation, there is minimal systemic absorption of dornase alfa; therefore, no measurable concentrations of dornase alfa would be expected in human milk. Advising patients/carers is the responsibility of the Respiratory Consultant.
Clinically relevant drug interactions
None. However, dornase alfa solution should not be mixed with other drugs or solutions in the nebuliser.
Precautions
Risk of bronchospasm on inhalation may be prevented or treated with a
selective b2 agonist or anticholinergic agent (this will be discussed with patient prior to starting treatment.
Containment of the aerosol is not necessary.
7. Special considerations
Supply, storage and reconstitution instructions
Dornase alfa nebuliser solution 1000 units (1mg) per mL vials (2.5mL) may be obtained by the patient’s community pharmacy from their wholesaler.
Store in a refrigerator at 2-8°C and protect from strong light. A single brief exposure to elevated temperatures (less than or equal to 24 hours at up to 30oC) does not affect product stability. Do not use after given expiry date.
Supply of ancillary equipment
Loan service will arrange to loan an appropriate nebuliser to the patient and maintain this equipment. NB This is a different nebuliser than that used for asthma treatment. Ultrasonic nebulisers may be unsuitable for delivery of dornase alfa because they may inactivate the product or have unacceptable aerosol delivery characteristics.
After each use, the nebuliser should be dismantled and cleaned as directed by the Manchester Adult Cystic Fibrosis Centre.
8. Back-up care available to GP from Hospital, including emergency contact procedures and help line numbers
For local decision
Manchester Adult Cystic Fibrosis Centre 0161 291 2015
Jan Redfern, CF Specialist Pharmacist: 0161 291 5082
Professor K Webb, Dr A Jones and Dr R Bright-Thomas (Respiratory Consultants, Manchester Adult Cystic Fibrosis Centre)
9. Statement of agreement
Shared care is an agreement between the GP and the Consultant. This form is a request by the consultant to share the suggested care pathway of your patient. If you are unable to agree to the sharing of care and initiating the suggested medication, please make this known to the consultant within 14 days, ideally stating the nature of your concern.
10. Written information provided to the patient
No information provided
11. Supporting References
Acknowledgement: Adapted from North Derbyshire Health Prescribing and Clinical Effectiveness Group (PACE)
Adapted from Greater Manchester Shared Care Guideline (Paediatrics)
References: BNF-C 2005, SPC Pulmozyme®
DORN 09 fnl