Download Growth Hormone - NHS Trafford CCG

GREATER MANCHESTER INTERFACE
PRESCRIBING GROUP
On behalf of the
GREATER MANCHESTER MEDICINES MANAGEMENT
GROUP
Reference Number
SHARED CARE GUIDELINE for the administration and
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monitoring of Growth Hormone (Somatropin) Treatment in
Children with Chronic Renal Insufficiency
Scope: Treatment of children with Growth Hormone
Classification
deficiency associated with Chronic Renal Insufficiency.
SHARED CARE GUIDELINE
Issue date: March 2007
Replaces October 2003 version
Author(s)/Originator(s)
To be read in conjunction with the
following documents
Authorised by
Review Date: March 2009
Dr.R.J.Postlethwaite, Ms.T.Smith, Ms.A.Adams
January 2000
Revised October 2003 - Dr. M. Bradbury, Ms. T.
Smith, Ms. K. O’Donnell
Amended March 6th 2007 – Hong Thoong Senior
Clinical Pharmacist – Renal
Summary of Product Characteristic and Patient
Information Leaflet for Genotropin®.
Royal Manchester Children’s Hospital Patient
Information Leaflet – “Growth Hormone therapy in
children on dialysis”
Interface Prescribing Group
Date: Mar 07
1. Introduction
Growth Hormone (GH), also known as somatropin, is a bioengineered
peptide made by recombinant DNA technology and does not carry a risk of
slow virus contamination. It is used as a substitutive therapy in GH
deficient states to promote growth and as an additive growth stimulant in
other forms of short stature, such as Turner Syndrome or chronic renal
insufficiency. It is licensed for use in the UK for poorly growing children
with GH insufficient states, chronic renal insufficiency, Turner Syndrome,
and in Prader-Wili syndrome for improvement of growth and body
composition.
It is given by daily subcutaneous injections usually administered by parent
or child (as in insulin therapy in diabetes).
Although biosynthetic GH has a good safety record it is an expensive
medication and its use should be thoroughly justified and carefully
monitored. The licence states that it can be prescribed by a doctor on
advice by a specialist, and these responsibilities have usually been
undertaken by the GP and a specialist paediatric endocrinologist. This is a
shared care protocol devised to co-ordinate these two responsibilities for
the maximal benefit and safety of the patient.
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2. Scope
Growth hormone (GH) may be considered for shared care arrangements
for substitutive therapy in patients with growth disturbances due to
insufficient secretion of GH associated with chronic renal insufficiency.
3. Clinical condition being treated
Referral Patterns Leading to GH Treatment
Children with chronic renal insufficiency are under hospital supervision by
paediatric nephrologists at the Manchester Children’s Hospitals NHS
Trust. As these children are very closely monitored in relation to their renal
problems, it is the paediatric nephrologist who refers patients to be
assessed for growth and decides on appropriate therapy.
A bi-monthly growth meeting attended by nephrology and endocrine teams
will assess patient growth and determine appropriate therapy.
It is considered that growth hormone treatment is necessary when:
a) Height velocity is less than the 25th centile for the child’s age looking
back over a one year period.
b) Height is below the third centile or drifting across the centiles.
If growth hormone is indicated then discussions with the parents and child
are necessary to assess the advantages and disadvantages of treatment
(please see the attached patient information sheets). The patient’s GP is
also informed of discussions.
The aim of therapy is a doubling of growth velocity if the growth velocity
was less than 4cm before starting growth hormone, or to increase growth
velocity by 2cm if the growth velocity was greater than 4cm before starting
growth hormone.
Response to growth hormone is assessed at growth meetings.
Growth hormone therapy is stopped if the response is deemed insufficient,
if the patient is non-compliant or when linear growth is complete.
4. Product information and treatment regimen to be used
Available Preparations
There are numerous GH preparations and presentations available.
However, for the purpose of this Shared Care Guideline, the current
formulary preparation (Genotropin®) will be the only one detailed below.
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Genotropin® (Pharmacia) is licensed for patients with chronic renal failure
and is available as 5.3mg and 12mg cartridges to be used in a peninjector device. The pen-injector device and needles are provided by the
hospital.
Genotropin® is also available as two-compartment single dose syringes
known as “MiniQuick injection”. They are available in the following
strengths: 0.2mg, 0.4mg, 0.8mg, 1.0mg, 1.2mg, 1.4mg, 1.6mg, 1.8mg and
2.0mg. However, cartridges are prescribed for the majority of patients.
At present a milligram of growth hormone costs approximately £20 (exc
vat). Examples of cost per annum:
20kg child
30kg child
£ 7,300
£10,950
(costs are approximate and are based on a dose of 0.05 mg/kg/day =
50micrograms/kg/day).
Dose of GH and Frequency of Injections
The dose of growth hormone is calculated according to body weight and is
administered by subcutaneous injection. The usual dose is
25micrograms/kg/day (0.025mg/kg/day) for two weeks increasing to
50micrograms/kg/day (0.050mg/kg/day). Injections are most biologically
effective when given daily so children have 7 injections per week.
5. Regimen Management
Roles of the Hospital Team
1. Confirmation of the diagnosis and justification to the GP for GH
indication. Need for GH is made on the basis of auxological and clinical
assessment.
2. Accurate initial auxology in order to provide baseline measures for
monitoring response to therapy.
3. Ensuring parents and child are aware of the advantages and
disadvantages of GH treatment so that an informed decision can be
made.
4. Seek confirmation that the patients’ GP will continue to prescribe GH.
5. Initial prescribing of GH (once agreed with GP) with provision of advice
to the GP on dose, frequency, and other details of administration.
6. Training of parents and/or patients in technique of GH administration.
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7. Accurate auxology during treatment so that response can be properly
audited, involving at least three out-patient visits per year.
8. Provide advice relating to concomitant treatment such as thyroxine, or
induction of puberty.
9. Scrutinise adverse medical events during treatment and assess any
possible causal relationship to GH.
10. Audit of response to therapy by comparison to national and international
standards.
11. Justification of continuation of GH and changes in dosage to the GP.
12. Provide support from the specialist renal nurse for the parents and child
and, where appropriate, the practice nurse.
Roles of the Primary Care Team
1. Continued prescribing of GH.
2. Report adverse medical events, which might be related to GH, to the
paediatric nephrologists.
3. Promote liaison of practice and specialist renal nurses.
4. Prescription of other therapy when indicated, e.g. vitamin D analogues
for bone disease, or hypotensive therapy.
6. Summary of cautions, contra indications, side-effects
Side-effects
As stated above, biosynthetic growth hormone is free from the problem of
slow virus or prion contamination which was associated with pituitary gland
derived GH. Generally, biosynthetic growth hormone has a good safety
record.
1. Headaches have been reported, especially in the early weeks of
treatment, which then usually resolve.
2. Benign intracranial hypertension has been reported and must be
distinguished from a simple headache. Usually headaches are more
severe and persistent and may be associated with visual symptoms,
and papilloedema may be present. Ceasing treatment will improve the
symptoms, usually immediately. Benign intracranial hypertension is
rare in comparison to simple idiopathic headache. However patients
with renal problems are more prone to this problem possibly due to fluid
retention. Current estimates suggest that about 2% of children with
renal problems who receive growth hormone develop this complication.
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3. High Blood Pressure: A small number of patients may develop high
blood pressure or existing high blood pressure may be worsened. This
is normally controlled by appropriate medication. If blood pressure is
very high or difficult to control, growth hormone may need to be
stopped.
4. Increased Blood Glucose: Children with a renal transplant and children
with renal failure are more likely than other children to have raised blood
glucose, and growth hormone has the potential to increase it further.
Despite this predisposition, the development of glucose intolerance is
rare/uncommon and responds to withdrawal of growth hormone.
5. Deterioration in Renal Function: Some studies suggest that patients
with chronic renal failure experience deterioration in renal function 2,3,
which is probably due to growth hormone treatment. Continued
deterioration of renal function usually stops if growth hormone is
discontinued. In renal transplants some reports have found that 5-10%
of children have an episode of rejection in the first year of treatment,
which is possibly related to the treatment. However, when transplant
function is measured at the beginning and end of the first year of
treatment there is no change in function and controlled trials of growth
hormone in patients with renal transplants have shown that there is no
increase in acute rejection. Any deterioration of renal function will be
discussed with the parents and child. Sometimes a child will continue
on growth hormone despite deterioration in renal function because
growth is so important for children with renal failure.
6. Bone disease: Bone disease (related to a number of factors including
reduced production of 1,25 dihydroxycholecalciferol, phosphate
retention and acidosis) is a common complication of renal failure. There
is clear evidence that this is made more severe in some patients on
growth hormone treatment. This is a particular problem after renal
transplant where steroid treatment to prevent rejection is a further risk
factor. The hip is the common joint involved.
a) Bone disease will be controlled before starting growth hormone
treatment.
b) X-Rays of the hips will be taken before starting treatment.
c) There will be careful clinical and biochemical monitoring for evidence of
worsening of the bone disease.
7. A lower dose of GH is used during the initial weeks of therapy to avoid
transient fluid retention.
8. Local injection site problems are rare/uncommon and may relate to the
vehicle rather than GH. Occasional lipoatrophy at injection sites has
been seen but this again is likely to resolve with time. Rotation of
injection site is undertaken to prevent this.
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Adverse Medical Events
Incidental illness of any kind is noted at the growth clinic and the GP is
encouraged to report such events to the hospital.
7. Special considerations
8. Back-up care available to GP from Hospital, including emergency
contact procedures and help line numbers
Contact Numbers
Consultant Paediatric Nephrologists: Dr.
Dr.
Dr.
Dr.
Bradbury
Lewis
Plant
Webb
(a) Nephrology Department - Manchester Children’s Hospital NHS Trust
Tel. 0161 922 2162 - ask to speak to one of the Consultants.
If it is out of hours phone the switchboard on 0161 794 4696 and ask for
the Registrar on call.
Specialist Renal Nurse:
Trish Smith
Tel.: via switchboard
Pharmacy Department - Manchester Children’s Hospitals NHS Trust
Tel.: 0161 922 2390
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
Growth Hormone Treatment in Children on Dialysis
Poor growth remains one of the major problems for children with kidney
failure particularly for those on dialysis. Growth can be improved by diet
and by various medications such as sodium bicarbonate and by dialysing
children well. Even so some children still grow poorly. It has now been
shown that 8 out of 10 (80%) of these poorly growing children respond to
Growth Hormone with improved growth.
How much will my child grow?
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Growth hormone treatment increases growth by at least 2 cm per year
and many children will grow even more than this. It might be difficult to
understand what this means for your own child and so your consultant will
show you on the growth chart the effect for your child. Unfortunately 1 out
of 5 will not show any useful improvement in growth.
What does treatment involve?
Growth Hormone is given by injection 7 days a week. We realise how
difficult it might be to think about having to give your child an injection.
You will be shown a video about this at an early stage which most
children and parents find helpful and reassuring. You will, of course, be
taught how to give injections and this teaching can be done at home to
avoid the need for extra visits to the clinic. There are many ways in which
we can help any children or parents who have problems in giving
injections.
What do parents and children think of Growth Hormone Treatment?
The injections are a burdensome extra task to take on and it is important
to discuss any problems you have with the staff. There are many ways in
which we can help if we know and even just talking about a problem is
often helpful. Parents recognise how important growth is for their child
and this helps with the extra burden. They are glad they have had the
opportunity to try Growth Hormone even if it does not improve growth in
their child.
If children have a realistic understanding of how much their growth is
likely to improve they are pleased when they respond to treatment.
Understandably if they do not grow they do show some disappointment
but again this is usually easy to deal with if we can talk about it.
Are there any side effects of treatment?
Every medication used to treat children has side effects. The question is
always, therefore, does the benefit from treatment outweigh the risks of
treatment. Growth Hormone has been used for many years in other
conditions and has now been extensively tested in children on dialysis.
The official bodies that decide whether or not treatment should be used
have approved Growth Hormone treatment in children on dialysis so they
obviously have been reassured by the rigorous testing that has been
carried out.
10 to 20% of patients experience some problems with Growth Hormone
treatment but in the majority these are minor such as pain or bruising at
the site of the injection.
There are four more serious problems you need to be aware of:1. High Blood Pressure. A small number of patients may develop
high blood pressure or existing high blood pressure may be
worsened. This is checked routinely in children on dialysis and
would be controlled by appropriate medication (or an increase in
medication if your child is already on blood pressure tablets) and
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adjustment of weight limits. If the blood pressure was very severe
and difficult to control it would be improved by stopping Growth
Hormone.
2. Increased Blood Sugar. Children on dialysis are more likely to
have increased blood sugars than normal children and Growth
Hormone could increase this further. Again this would be detected
by the routine blood tests done in dialysis patients. The blood
sugar would return to normal if the Growth Hormone was stopped
or if it was decided to carry on with Growth Hormone the blood
sugar would easily controlled by insulin.
3. Headaches. At the start of treatment it is common for children to
complain of more headaches than normal. These headaches are
usually mild and disappear after children adapt to the treatment. If
the headaches occur every day, become progressively more
severe or are associated with blurring of vision it is important this
is reported to the nephrology unit. In these rare circumstances
treatment may need to be stopped and the restarted in a lower
dosage.
4. Bone disease. This is a problem for almost all children on dialysis
who will be receiving some form of Vitamin D and often calcium
carbonate. This problem needs even more careful attention in
patients on Growth Hormone.
How do I get supplies of Growth Hormone?
The hospital will give you an initial supply of Growth Hormone to start
you off and then you will normally get further supplies from your local
pharmacy. Growth Hormone is not usually stocked by local
pharmacies and it takes a few days to order it. It is important,
therefore, to take a prescription to the pharmacy as soon as possible to
make sure there is no interruption in supplies.
Dr.R.J.Postlethwaite
Ms.T.Smith
Ms.A.Adams
January 2000
Revised by Dr M. Bradbury
Ms T Smith
Ms K.O’Donnell
October 2003
11. Supporting References
1
genotropin Summary of Product Characteristics. Electronic
Medicines Compendium [www] http://emc.medicines.org.uk/ (Date last
updated on eMC: 13th Dec 2006
2
Fine RN, Yadin O, Moulten L, Nelson PA, Boechat MI, Lippe
BH. Extended recombinant human growth hormone treatment after
renal transplantation in children. J Am Soc Nephrol
1992;2(suppl):S274-83
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3
Benfield MR, Parker KL, Waldo FB, Overstreet SL, Kohaut EC.
Growth hormone in the treatment of growth failure in children with
renal transplantation. Kidney Int 1993;44(suppl): S62-4
4
Mentser M, Breen TJ, Kenneth Sullivan E, Fine R. Growth
hormone treatment of renal transplant recipients: The National
Cooperative Growth Study experience – A report of the National
Cooperative Growth Study and the North American Pediatric Renal
Transplant Cooperative Study. J Paediatr 131(1): S20-24
5
Fine RD (1998) Growth hormone in children with chronic renal
insufficiency and end-stage renal disease. Endocrinologist 8(3): 160169
6
Kitagawa T, Ito K, Ito H, Sakai T, Wada H, Kajwara (1997). GH
Treatment of Children With Chronic Renal Insufficiency: A Japanese
Clinical Trial. Clin Paediatr Endocrinol 6 (suppl 10): 73-80
7
Fine R (1997). Recombinant human growth hormone (rhGH)
treatment in children with chronic renal insufficiency (CRI). Clin
Paediatr Endocrinol 6 (suppl10): 69-72
8
Yadin O, Fine R (1997). Long-term use of recombinant human
growth hormone in children with chronic renal insufficiency. Kidney Int
Suppl 51 (58): S114-117
9
Fine R, Kohaut E, Brown D, Kuntze J, Attie KM (1996). Longterm treatment of growth retarded children with chronic renal
insufficiency, with recombinant human growth hormone. Kidney Int 49
(3): 781-785
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