Guidelines for the Administration and Monitoring of Human Growth Hormone (Somatropin) Treatment in Children with Chronic Renal Insufficiency.

Transcription

1 Manchester Children s Hospitals NHS Trust Guidelines for the Administration and Monitoring of Human Growth Hormone (Somatropin) Treatment in Children with Chronic Renal Insufficiency. These guidelines were adopted by the East Lancashire Medicines Management Board in March 2005 for use across the East Lancashire Health Economy. 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 (Review October 2005) 1

2 Guidelines for the Administration and Monitoring of Human Growth Hormone Treatment (Somatropin) in Children with Chronic Renal Insufficiency 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, and Turner Syndrome. 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. 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 jointly by the nephrology and endocrine teams, assess patient s growth and decide on appropriate therapy. It is considered that growth hormone treatment is necessary when: a) Height velocity is less than the 25 th 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 a child required growth hormone, discussions with the parents and child are necessary to look at the advantages and disadvantages of the treatment. (Please see attached Patient Information sheets). The patient s GP is also informed of the discussions. 2

3 The aim is to double the 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. Assessment of the response to growth hormone is monitored at the bi-monthly growth meetings. Growth hormone is stopped if the response is deemed insufficient, if the patient is non-compliant or when linear growth is complete. 3

4 Roles of the Hospital Team 1. Confirmation of the diagnosis and justification to the GP that GH is indicated. Need for GH is made on the basis of auxological and clinical assessment. 2. Accurate initial auxology in order to provide baseline for monitoring of growth response. 3. Ensuring parents and child are aware of the advantages and disadvantages of GH treatment, so that an informed decision can be made. 4. Confirmation that the GP is willing to continue prescribing GH. 5. Initial prescribing of GH (once agreed with GP) with advice to the GP on dose, frequency of injections, and details of administration. 6. Training of parents and/or patients in technique of GH injection (comparable to the administration of insulin in diabetic children). 7. Accurate auxology during treatment so that response can be properly audited. This involves at least three out-patent visits per annum. 8. Advice related to concomitant treatment, such as thyroxine, or induction of puberty. 9. Scrutiny of adverse medical events during treatment and assessment of possible causal relationship to GH. 10. Audit of response by comparison with national/international standards. 11. Justification of continuation of GH and changes in dosage to the GP. 12. Support for the parents and child, and where appropriate for the practice nurse, from the specialist renal nurse. Roles of the Primary Care Team 1. Continued prescribing of growth hormone. 2. Reporting of adverse medical events which might be side effects of GH, to paediatric nephrologist. 3. Liaison of practice nurse with specialist renal nurse. 4. Prescription of other therapy when relevant, eg. Vitamin D metabolites for bone disease, hypotensive agents. 4

5 More Information on Human Growth Hormone (somatropin) Available Preparations Genotropin (Pharmacia) is licensed for patients with chronic renal failure and is available as 12mg cartridges to be used in a pen-injector device. The pen-injector device and needles are provided by the hospital. Cost At present a milligram of growth hormone costs approximately (exc vat). Examples of cost per annum: 20kg child 8,500 30kg child 12,700 (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 recommended according to body weight and is given 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. Side-effects As stated above, biosynthetic growth hormone is free from the problem of slow virus (or prior) contamination, which tragically affected pituitary derived growth hormone. Biosynthetic growth hormone has a good safety record. Adverse medical events (incidental illnesses) have been reported although few are likely to be causally related. 1. Headaches have been reported, especially in the early weeks of treatment, which then usually resolve. 2. Benign Intracranial Hypertension has been reported and has to be distinguished from simple headache as above. Usually the headaches are more severe and persistent and may be associated with visual symptoms. Papilloedema may be present. Stopping treatment will improve the symptoms, usually immediately. We have described this problem in detail and disproportionate to its incidence, because it must be distinguished from commonly occurring simple headache. Patients with renal problems are more prone to this problem probably because of fluid retention. Current estimates suggest that about 2% of children with renal problems who receive growth hormone develop this complication. 3. High Blood Pressure: A small number of patients may develop high blood pressure or existing high blood pressure may be worsened. This would normally be controlled by appropriate medication. If the blood pressure was very high or difficult to control, growth hormone may be stopped. 5

6 4. Increased Blood Glucose: Children with a renal transplant and children with renal failure are more likely than normal children to have raised blood glucose and growth hormone could increase it further. Despite this predisposition the development of glucose intolerance has been very low and responds to withdrawal of growth hormone. 5. Deterioration in Renal Function: Studies suggest that 2-3% of patients with chronic renal failure experience deterioration in renal function, which is probably due to growth hormone treatment. This deterioration 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. Transient fluid retention in the first few days/weeks can occur. A lower dose is used in the initial few weeks to avoid this. 8. Local injection site problems are few and may relate to the vehicle rather than growth hormone. Occasional lipoatrophy at injection sites has been seen but this again is likely to resolve with time. Adverse Medical Events Incidental illness of any kind is noted in the growth clinic and the GP is encouraged to report such events to the hospital. 6

7 Contact Numbers Consultant Paediatric Nephrologists: Dr. Bradbury Dr. Lewis Dr. Plant Dr. Postlethwaite Dr. Webb Nephrology Department - Manchester Children s Hospital NHS Trust Tel ask to speak to one of the Consultants. If it is out of hours phone the switchboard on and ask for the Registrar on call. Specialist Renal Nurse: Tel. No: Trish Smith Pharmacy Department - Manchester Children s Hospitals NHS Trust Tel. No

8 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? 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 you 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 off 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. 8

9 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 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. 9

10 Growth Hormone Treatment in Children with Kidney Failure Poor growth remains one of the major problems for children with kidney failure. Growth can be improved by diet and by various medications such as sodium bicarbonate. 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? 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 you 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 off 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 10

11 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 with kidney failure. 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 five 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 when you attend outpatients (or an increase in medication if your child is already on blood pressure tablets). 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 with kidney failure 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 outpatients. 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 many children with kidneyl failure who will often be receiving some form of Vitamin D and often calcium carbonate. This problem needs even more careful attention in patients on Growth Hormone. 5. Worsening of kidney function. This is, of course, the most worrying possibility. Studies suggest that about 2 to 3% of children show worsening in kidney function that is probably related to Growth Hormone Treatment. This deterioration usually stops if Growth Hormone is discontinued. The deterioration will not be rapid and so there will be time to discuss the correct approach to this problem for your child. It is worth stressing that if children with kidney failure are not growing well that we will often discuss early transplantation with you. Sometimes, therefore, our advice will be to continue with Growth Hormone even if there is worsening kidney function. This is because growth is so important for children with kidney failure. 11

12 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. 12

13 Dr.R.J.Postlethwaite Ms.T.Smith Ms.A.Adams Revised by Dr M. Bradbury Ms T Smith Ms K.O Donnell January 2000 October 2003 (Review October 2005) 13