Revised Guidelines endorsed by the by O998zF0H

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									                Guidelines for the
           Pharmaceutical Benefits Scheme
             Growth Hormone Program
         The Pharmaceutical Benefits Scheme Growth Hormone Program is governed
         by the National Health (Growth Hormone Program) Special Arrangement 2011
         (PB 88 of 2011) which is a special arrangement made under section 100 of the
         National Health Act 1953.




Effective from: April 2012

Available at http://www.health.gov.au/hgh
Table of Contents
1. DEFINITIONS, ACRONYMS, DATA ............................................................................ 3
2. THE PHARMACEUTICAL BENEFITS SCHEME GROWTH HORMONE
PROGRAM ................................................................................................................................ 5
  2.1  Aims of the PBS Growth Hormone Program .............................................................. 6
  2.2  Purpose of this document ............................................................................................. 6
3. ELIGIBILITY CRITERIA FOR SUBSIDISED TREATMENT .................................. 7
  3.1  Common requirements for all patients ......................................................................... 7
  3.2  Short stature and slow growth...................................................................................... 8
  3.3  Biochemical growth hormone deficiency .................................................................... 9
  3.4  Growth retardation secondary to an intracranial lesion or cranial irradiation ........... 10
  3.5 Neonates/infants at risk of hypoglycaemia secondary to growth hormone deficiency11
  3.6  Turner Syndrome ....................................................................................................... 13
  3.7  Short stature due to short stature homeobox (SHOX) gene disorders ....................... 14
  3.8  Chronic renal insufficiency ........................................................................................ 15
  3.9  Growth hormone deficiency and precocious puberty ................................................ 16
  3.10 Prader-Willi Syndrome .............................................................................................. 17
  3.11 Exclusion criteria for initial and continuing treatment .............................................. 19
  3.12 Recommencement criteria ......................................................................................... 20
  3.13 Reclassification arrangements ................................................................................... 20
4. DOSAGE ........................................................................................................................... 21
  4.1  Dosing overview ........................................................................................................ 21
  4.2  Starting dose............................................................................................................... 22
  4.3  Continuing dose ......................................................................................................... 22
5. ADMINISTRATIVE ARRANGEMENTS .................................................................... 24
  5.1  Initial treatment .......................................................................................................... 24
  5.2  Continuing treatment ................................................................................................. 25
  5.3  Supply of growth hormone ........................................................................................ 25
  5.4  Dispensing of growth hormone.................................................................................. 26
  5.5  Patients travelling overseas ........................................................................................ 26
  5.6  Compliance with the administration of growth hormone treatment .......................... 27
  5.7  OZGROW                                                                                                  ....................... 28
  5.8  Review of decisions ................................................................................................... 28
  5.9  Role of the Growth Hormone Advisory Committee .................................................. 29
  5.10 Departmental details .................................................................................................. 30
6. ATTACHMENTS ............................................................................................................ 31
  6.1  Growth hormone preparations available as a pharmaceutical benefit ....................... 31
  6.2  Storage of Growth Hormone ...................................................................................... 32
  6.3  Brand prescribing restrictions based on approved eligibility category ...................... 33
  6.4  Evaluation of response to treatment and corresponding dose for PWS patients ....... 34




Guidelines for the PBS Growth Hormone Program                                                                              2
1. DEFINITIONS, ACRONYMS, DATA
10th adult height centile      Boys: 167.66cm         Girls: 155.02cm

Abnormally low growth          Growth velocity below the 25th centile for bone age and sex, as
velocity                       determined by reference to the charts of Tanner and Davies,
                               published in the European Journal of Paediatrics, September
                               1985, vol 107, No 3, p 317-319.

Absolute dose                  mg/wk.

Biochemical growth             Peak serum growth hormone concentration < 10mU/L in
hormone deficiency             response to:
(BGHD)                         2 pharmacological tests (eg arginine, clonidine, glucagon,
                               insulin)
                                                              or
                               1 pharmacological test AND 1 physiological test (eg sleep,
                               exercise)
                                                              or
                               1 test (pharmacological or physiological) WITH other evidence
                               of growth hormone deficiency such as structural CNS
                               abnormalities known to be associated with growth hormone
                               deficiency or low plasma IGF-1 ± IGFBP-3 levels

BMI                            Body mass index.

BSA                            Body surface area. BSA is calculated using the most recent
                               height and weight measurements.

CDC                            Centers for Disease Control and Prevention, US Department of
                               Health and Human Services.

Chronic renal insufficiency Estimated glomerular filtration rate (GFR) less than 30
                            ml/minute/1.73 m2. Estimates of GFR are usually made using
                            the Schwartz equation.
Constitutional/                Refers to a situation in which:
Maturational delay in            the onset of puberty is delayed (beyond 12 years in girls or
growth and puberty                 14 years in boys); and/or
                                 growth velocity is below the 25th centile for bone age and
                                   sex; and
                                 there is absence of any evidence of pathological conditions
                                   (identified through clinical tests such as growth hormone
                                   stimulation tests, TSH, FT4, Coeliac screening,
                                   Karyotype); and
                                 bone age is delayed by 2 years or more; and
                                 the estimated final height is within the normal range and
                                   within the expectations for the family (target height range:
                                   +/- 7.5cm from MPH for boys and +/- 6.0cm from MPH
                                   for girls).



Guidelines for the PBS Growth Hormone Program                                         3
Dose                           mg/m2/wk.

DTPA                           Diethylenetriamene penta-acetate.

GHAC                           Growth Hormone Advisory Committee.

Morbid obesity                 Body weight greater than 200% of ideal body weight for height
                               based on CDC 2000 data. Ideal body weight is derived by
                               calculating the 50th percentile weight for height.

MPH                            Mid parental height.

‘Older child’                  Older boy: chronological age > = 14.5 years or
                               bone age > = 12.5 years
                               Older girl: chronological age > = 12.5 years or
                               bone age > = 10.5 years

PBAC                           Pharmaceutical Benefits Advisory Committee.

PBS                            Pharmaceutical Benefits Scheme.

Precocious puberty             Girls: The onset of puberty before the chronological age of 8,
                               demonstrated by Tanner stage 2 breast or pubic hair
                               development; or the onset of menarche before the age of 10.
                               Boys: The onset of puberty before the chronological age of 9,
                               demonstrated by Tanner stage 2 genital or pubic hair
                               development or testicular volumes ≥ 4mls.

SDS                            Standard deviation score.

Short stature                  Height below the 1st centile for age, measured using the Centers
                               for Disease Control and Prevention growth charts, available at
                               www.cdc.gov/growthcharts/.

Skeletal maturity              Bone age > =13.5 years (female) or > = 15.5 years (male). This
                               skeletal maturity represents 97.5% of estimated final height.

Turner Syndrome – growth Height at or below the 95th centile on the Turner specific chart
curve for girls          as determined by reference to Lyon et al, 1985, Growth curve
                         for girls with Turner Syndrome, Archives of Disease in
                         Childhood, vol 60, p 932-935.

Turner Syndrome – Ranke        Referenced from Ranke et al, 1983, European Journal of
growth velocity chart          Paediatrics, vol.141, p 81-88, Figure 4: Mean height velocities
                               in patients with Turner syndrome observed by different
                               investigators.

Untreated PWS standards        Reference from Butler et al, 1991, Standards for Selected
                               Anthropometric Measurements in Prader-Willi Syndrome,
                               Paediatrics, vol 88, No 4, p853-860.




Guidelines for the PBS Growth Hormone Program                                          4
2.    THE PHARMACEUTICAL BENEFITS SCHEME
      GROWTH HORMONE PROGRAM
Growth Hormone (GH) is subsidised by the Australian Government through the
Pharmaceutical Benefits Scheme (PBS). In addition to the drugs and medicinal preparations
available under normal PBS arrangements, GH is available through special PBS arrangements
made by the Minister under section 100 of the National Health Act 1953. The supply of GH
under section 100 of the Act is provided for in the National Health (Growth Hormone)
Special Arrangement 2011 (PB 88 of 2011).

The PBS GH Program is administered by the Australian Government Department of Health
and Ageing, with the assistance of the Growth Hormone Advisory Committee (GHAC), a
panel of experienced specialist paediatric endocrinologists and paediatricians.

GH has a variety of biological actions in the newborn baby, child and adolescent. These can
be classified as:
     Growth-promoting
     Metabolic

Growth-promoting effects of GH are seen in individual organs, but are best recognised by
increases in body length or height, which is the conventional measured end-point. This
effect, via promotion of bone growth, ceases when bone growth plates fuse late in puberty.
Following these events, GH is no longer effective in promoting linear growth.

Metabolic effects of GH include protection from hypoglycaemia, breakdown of fat and
enhanced muscle growth, and support of bone mineralisation. These effects persist
throughout life.

The PBS GH Program is primarily concerned with the growth-promoting effects of GH,
namely enhancement of linear growth. In addition, the program allows for the indication of
neonatal hypoglycaemia associated with growth hormone deficiency. With the addition of
Prader-Willi Syndrome to the GH Program in 2009, the program is now also focused on
improving body composition for patients with Prader-Willi Syndrome.




Guidelines for the PBS Growth Hormone Program                                       5
2.1 Aims of the PBS Growth Hormone Program
The Broad Aim of the PBS Growth Hormone (GH) Program is to allow a trial of treatment
with GH and possible ongoing GH therapy in children who are likely to achieve benefits as
listed below under Specific Aims.

The Specific Aims of GH therapy for children are as follows:
      To promote short-term catch-up growth in children of short stature;
      To enhance long-term linear growth in children of short stature;
      To allow children to achieve their familial genetic adult height potential, and where
       possible to achieve a final height within the normal population range;
      To correct neonatal hypoglycaemia due to GH deficiency;
      To ensure GH therapy is safe; and
      To improve linear growth and body composition for patients with Prader-Willi
       Syndrome.


2.2 Purpose of this document
The Department of Health and Ageing uses the National Health (Growth Hormone Program)
Special Arrangement 2011 (PB 88 of 2011) to administer the PBS GH Program, including the
determination of eligibility for subsidised GH treatment.

As these Guidelines are consistent with PB 88 of 2011, they provide a framework and advice
for clinicians who wish to apply for PBS subsidised GH for their patients.

The Guidelines may also be of interest to patients’ families.




Guidelines for the PBS Growth Hormone Program                                         6
3. ELIGIBILITY CRITERIA FOR SUBSIDISED
   TREATMENT
3.1 Common requirements for all patients
   a) The patient must be, or be treated as, an ‘eligible person’ within the meaning of the
      Health Insurance Act 1973. An eligible person includes an Australian resident, an
      eligible overseas representative and an eligible overseas visitor entitled to receive
      subsidised PBS medicine through a Reciprocal Health Care Agreement.
       Note: patients that are, or are treated as, eligible persons are entitled to Medicare benefits. Patients can
       check whether they are entitled to Medicare benefits with Medicare Australia.

   b) For applications under all categories excluding section 3.10, a minimum of 12 months
      of recent growth data (height and weight measurements) must be submitted with the
      initial application at intervals of no greater than six months; or

       Six months of data will be accepted if treatment is sought urgently in older children
       (refer to section 1 for definition); or

       Applications that do not fulfil the data requirement above, but have previous consistent
       height data may be considered by the Department and/or the GHAC based on their
       merit; and

   c) The most recent data set should be no more than 3 months old at the time of
      application; and

   d) A bone age reading taken within the last 12 months must be submitted (not mandatory
      if the patient is less than 2.5 years of chronological age); and

   e) Applications for initial treatment must be submitted using the Application for initial
      supply of growth hormone form or the Application for initial supply of growth
      hormone for the treatment of Prader-Willi Syndrome form, ensuring that all required
      data, including that mentioned above, is provided. A covering letter, setting out the
      patient’s medical history, social history, investigations and concurrent medications
      must also be submitted with all new applications.

   f) Applicants are encouraged to refer to application checklists relevant to each eligibility
      category, to identify the information required with the application. Application forms
      and data checklists are available from the Department’s website:
      www.health.gov.au/hgh.

   Note: Clinicians are encouraged to seek biochemical evidence of subnormal pituitary
   growth hormone secretion unless a clear alternative diagnosis (eg 3.6, 3.7, 3.8 and 3.10)
   has been made. Assessment of thyroid, adrenocortical, gonadal and neurohypophyseal
   function and exclusion of other chronic diseases should be undertaken and appropriate
   replacement therapy commenced prior to the introduction of GH therapy.

   Note: Some conditions may not demonstrate significant response to growth hormone, e.g.
   older patients with thalassaemia and individuals with skeletal dysplasia. Prescribers
   should take this into consideration when making initial applications or applying for
   continued growth hormone therapy.



Guidelines for the PBS Growth Hormone Program                                                            7
3.2 Short stature and slow growth
3.2.1 Eligibility criteria

Both of the following criteria must be met in order to be eligible for GH treatment under the
category of short stature and slow growth:

    a) Current height below the 1st centile for age and sex; and

    b) Growth velocity below the 25th centile for bone age and sex, measured at both
       12 month and 6 month intervals.

3.2.2 Exceptions when applications will be referred to the GHAC

    a) All children with a chronological age or bone age of less than 2.5 years will be
       referred by the Department to the GHAC for clinical assessment, regardless of whether
       they meet criteria 3.2.1a and/or 3.2.1b as described above; or

    b) Patients with constitutional or maturational delay who have an estimated mature height
       below the 1st centile.

3.2.3 Continuation criteria

Subsidised treatment can continue unless one or more of the following applies:

    a) The patient has reached skeletal maturity; and/or

    b) The patient’s height is equivalent to or above the 10th adult height centile; and/or

    c) The patient has failed to meet any of the response criteria listed at section 4.3.1 while
       on maximum dose for the last 6 month treatment period AND has failed to achieve
       and maintain mid parental height SDS1; and/or

    d) The decision is made to cease GH treatment. The following information should be
       provided in this instance:

                Date of cessation;
                Reason for cessation;
                Final measurements at the time of cessation; and
                Quantity of GH supplies remaining at the patient’s delivery point.




1
 The treating doctor should inform the Department if there were any circumstances during the last treatment
period that may have impacted on the effectiveness of GH treatment. This will be taken into consideration when
assessing the patient’s response to treatment.

Guidelines for the PBS Growth Hormone Program                                                       8
3.3 Biochemical growth hormone deficiency
3.3.1 Eligibility criteria

All of the following criteria must be met in order to be eligible for GH treatment under the
category of biochemical growth hormone deficiency:

    a) Current height below the 1st centile for age and sex; and

    b) Growth velocity below the 25th centile for bone age and sex measured at both
       12 month and 6 month intervals2; and

    c) Evidence of biochemical growth hormone deficiency (refer to Section 1 for definition).

    Note: Sex-steroid priming prior to growth hormone testing may be useful in
    discriminating between constitutional delay and growth hormone deficiency.

3.3.2 Exceptions when applications will be referred to the GHAC

    a) Children that meet criteria 3.3.1 b and c, but have a height above the 1st centile; or

    b) Children that meet criteria 3.3.1a and c, have a bone age of less than 2.5 years and
       an annual growth velocity of greater than 8cm per year.

3.3.3 Continuation criteria

Subsidised treatment can continue unless one or more of the following applies:

    a) The patient has reached skeletal maturity; and/or

    b) The patient has failed to meet any of the response criteria listed at section 4.3.1 while
       on maximum dose for the last 6 month treatment period AND has failed to achieve and
       maintain mid parental height SDS3; and/or

    c) The decision is made to cease GH treatment. The following information should be
       provided in this instance:

                 Date of cessation
                 Reason for cessation
                 Final measurements at the time of cessation
                 Quantity of GH supplies remaining at the patient’s delivery point.




2
  Growth velocity for bone age cannot be determined in children with a bone age of less than 2.5 years. Children
who meet criteria 3.3.1a and 3.3.1c, and have a bone age of less than 2.5 years, will be approved for treatment if
their annual growth velocity is equal to or less than 8cm per year.
3
  The treating doctor should inform the Department if there were any circumstances during the last treatment
period that may have impacted on the effectiveness of GH treatment. This will be taken into consideration when
assessing the patient’s response to treatment.

Guidelines for the PBS Growth Hormone Program                                                           9
3.4 Growth retardation secondary to an intracranial lesion or cranial
    irradiation
Children suffering from growth retardation secondary to an intracranial lesion (eg.
craniopharyngioma) or cranial irradiation for neoplasia, now in remission, will be eligible
for treatment if all of the following criteria are met:

3.4.1 Eligibility criteria

    a) Evidence of biochemical growth hormone deficiency; and

    b) Growth velocity below the 25th centile for bone age and sex measured at both
       12 month and 6 month intervals4; and

    c) 12 months of observation has occurred following the completion of treatment (eg
       surgery, chemotherapy and/or radiotherapy), or, if the patient’s treating practitioner
       advised that it was not safe to treat the lesion, 12 months of observation has occurred
       since the lesion was diagnosed..

3.4.2 Exceptions when applications will be referred to the GHAC

    a) Children who have received cranial irradiation in excess of 30 Gy and meet criteria
       3.4.1b and c, but do not meet criteria 3.4.1a; or

    b) Children that meet criteria 3.4.1a and c, have a bone age of less than 2.5 years and
       an annual growth velocity of greater than 8cm per year; or

    c) Children that do not meet criteria 3.4.1c.

3.4.3 Continuation criteria

Subsidised treatment can continue unless one or more of the following applies:

    a) The patient has reached skeletal maturity; and/or

    b) The patient has failed to meet any of the response criteria listed at section 4.3.1 while
       on maximum dose for the last 6 month treatment period AND has failed to achieve
       and maintain mid parental height SDS5; and/or

    c) The decision is made to cease GH treatment. The following information should be
       provided in this instance:

                 Date of cessation;
                 Reason for cessation;
                 Final measurements at the time of cessation; and
                 Quantity of GH supplies remaining at the patient’s delivery point.


4
  Growth velocity for bone age cannot be determined in children with a bone age of less than 2.5 years. Children
who meet criteria 3.3.1a and 3.3.1c, and have a bone age of less than 2.5 years, will be approved for treatment if
their annual growth velocity is equal to or less than 8cm per year.
5
  The treating doctor should inform the Department if there were any circumstances during the last treatment
period that may have impacted on the effectiveness of GH treatment. This will be taken into consideration when
assessing the patient’s response to treatment.

Guidelines for the PBS Growth Hormone Program                                                         10
3.5 Neonates/infants at risk of hypoglycaemia secondary to growth
    hormone deficiency
If the treating doctor is concerned about the risk of hypoglycaemia in the first two years of
life, urgent approval of the application may be requested. The application should be faxed to
the Department marked ‘urgent’. It is also recommended to phone the Department to advise
that an urgent application has been submitted.

The cost of immediate in-patient treatment must be covered by the hospital. An application
should be submitted to the Department for approval of subsidised GH treatment for
commencement following discharge from hospital.

3.5.1 Eligibility criteria

The following criteria must be met in order to be eligible for GH treatment under the
category of Hypoglycaemia:

    a) Neonates/infants under 2 years of age with documented hypoglycaemia, or who are at
       risk of hypoglycaemia, secondary to growth hormone deficiency.

3.5.2 Exceptions when applications will be referred to the GHAC

    a) All initial applications submitted under this category will be referred by the
       Department to the Chair of the GHAC for urgent clinical assessment.

        The following data must be specifically addressed in a covering letter accompanying
        the initial application form:

                  i. Biochemical data. Including serum concentrations of growth hormone and
                     cortisol during hypoglycaemia and serum concentrations of FT4 and TSH.
                  ii. Clinical risk factors. Including for example: birth asphyxia, breech birth, severe
                      central nervous system (CNS) infection, midline CNS defect or tumour.
                 iii. Clinical evidence of pituitary insufficiency. Including for example: prolonged
                      neonatal jaundice, neonatal hypoglycaemia or history suggestive of subsequent
                      hypoglycaemia, temperature instability. Evidence of a mid-line defect such as
                      cleft palate, high arched palate or mid-facial hypoplasia, presence of
                      micropenis, documented diabetes insipidus.
                 iv. Radiological findings. Results of CNS imaging should accompany the
                     application if available, but must be provided within 5 years of commencing
                     treatment to allow for review by the GHAC as noted at 3.5.2a).

    b) Once the patient reaches 5 years of chronological age, the case will be referred to the
       GHAC for clinical assessment. Depending on the patient’s response to treatment, and
       the clinical, biochemical and radiological evidence available, the GHAC will either
       recommend reclassification of the patient as biochemical growth hormone deficient,
       ask for further evaluation of the hypothalamic/pituitary axis, or recommend that
       treatment be ceased.

    c) Applications for continuing treatment will be referred by the Department to the GHAC
       for advice if continuation criterion 3.5.3 applies.




Guidelines for the PBS Growth Hormone Program                                                11
3.5.3 Continuation criteria

Subsidised treatment can continue unless one or more of the following applies:

    a) The patient has reached 5 years of chronological age, after which time eligibility for
       continued growth hormone treatment will be determined by the Department (refer to
       criteria 3.5.2b for details); and/or

    b) The patient has failed to meet any of the response criteria listed at section 4.3.1 while
       on maximum dose for the last 6 month treatment period AND has failed to achieve and
       maintain mid parental height SDS6; and/or

    c) The decision is made to cease GH treatment. The following information should be
       provided in this instance:

                Date of cessation;
                Reason for cessation;
                Final measurements at the time of cessation; and
                Quantity of GH supplies remaining at the patient’s delivery point.




6
 The treating doctor should inform the Department if there were any circumstances during the last treatment
period that may have impacted on the effectiveness of GH treatment. This will be taken into consideration when
assessing the patient’s response to treatment.

Guidelines for the PBS Growth Hormone Program                                                      12
3.6 Turner Syndrome
3.6.1 Eligibility criteria

All of the following criteria must be met in order to be eligible for GH treatment under the
category of Turner Syndrome:

    a) Current height at or below the 95th centile on the Turner Syndrome growth curve for
       girls derived from Lyon et al; and

    b) Not exhibiting significant catch-up growth:

                 i) growth does not upwardly cross height centiles with reference to the Turner
                    Syndrome growth curve above; or

                 ii) growth velocity of less than the 25th percentile for bone age and sex7; and

    c) Diagnostic results consistent with Turner Syndrome and a copy of the laboratory result
       provided with the initial application.

3.6.2 Exceptions when applications will be referred to the GHAC

    a) Children that meet criteria 3.6.1a and c, have a bone age of less than 2.5 years and an
       annual growth velocity of greater than 8 cm per year.

3.6.3 Continuation criteria

Subsidised treatment can continue unless one or more of the following applies:

    a) The patient has reached skeletal maturity; and/or

    b) The patient’s height is equivalent to or above the 10th adult height centile; and/or

    c) The patient has failed to meet any of the response criteria listed at section 4.3.1 at
       maximum dose for the last 6 month treatment period AND the patient’s growth
       velocity for bone age is below the mean growth velocity of untreated Turner
       Syndrome girls (Ranke et al)8; and/or

    d) The decision is made to cease GH treatment. The following information should be
       provided in this instance:

                Date of cessation;
                Reason for cessation;
                Final measurements at the time of cessation; and
                Quantity of GH supplies remaining at the patient’s delivery point.




7
  Determined by reference to the charts of Tanner and Davies, published in the European Journal of Paediatrics,
September 1985, vol 107, No 3, p 317-319.
8
  The treating doctor should inform the Department if there were any circumstances during the last treatment
period that may have impacted on the effectiveness of GH treatment. This will be taken into consideration when
assessing the patient’s response to treatment.

Guidelines for the PBS Growth Hormone Program                                                      13
3.7 Short stature due to short stature homeobox (SHOX) gene disorders
3.7.1 Eligibility criteria

All of the following criteria must be met in order to be eligible for GH treatment under the
category of SHOX disorders:

    a) Current height below the 1st centile for age and sex; and

    b) Growth velocity below the 25th centile for bone age and sex measured at both
       12 month and 6 month intervals9; and

    c) Diagnostic results consistent with SHOX mutation/deletion, including mosaic sex
       chromosome abnormalities (which include 45XO cell lines). A copy of the laboratory
       result must be provided with the initial application.

3.7.2 Exceptions when applications will be referred to the GHAC

    a) Children that meet criteria 3.7.1a and c, have a bone age of less than 2.5 years and an
       annual growth velocity of greater than 8 cm a year.

3.7.3 Cessation criteria

Subsidised treatment can continue unless one or more of the following applies:

    a) The patient has reached skeletal maturity; and/or

    b) The patient’s height is equivalent to or above the 10th adult height centile; and/or

    c) The patient has failed to meet any of the response criteria listed at section 4.3.1 while
       on maximum dose for the last 6 month treatment period AND has failed to achieve
       and maintain mid parental height SDS10; and/or

    d) The decision is made to cease GH treatment. The following information should be
       provided in this instance:

                 Date of cessation;
                 Reason for cessation;
                 Final measurements at the time of cessation;
                 Quantity of GH supplies remaining at the patient’s delivery point.




9
  Growth velocity for bone age cannot be determined in children with a bone age of less than 2.5 years. Children
who meet criteria 3.7.1a and 3.7.1c, and have a bone age of less than 2.5 years, will be approved for treatment if
their annual growth velocity is equal to or less than 8cm per year.
10
   The treating doctor should inform the Department if there were any circumstances during the last treatment
period that may have impacted on the effectiveness of GH treatment. This will be taken into consideration when
assessing the patient’s response to treatment.

Guidelines for the PBS Growth Hormone Program                                                         14
3.8 Chronic renal insufficiency
3.8.1 Eligibility criteria

Children with chronic renal insufficiency will be eligible for subsidised GH treatment if all
of the following criteria are met:
     a) Current height equal to or less than the 25th centile for age and sex; and

     b) Growth velocity equal to or less than the 25th centile for bone age and sex, measured at
        both 12 month and 6 month intervals11; and

     c) An estimated glomerular filtration rate (GFR) less than 30 ml/minute/1.73 m2,
        measured by creatinine clearance, excretion of radionuclides such as DTPA, or by the
        height/creatinine formula. The treating physician must clarify which method is used to
        calculate GFR and to provide the result in the correct units; and

     d) 12 months has lapsed since renal transplant (if applicable).

3.8.2 Exceptions when applications will be referred to the GHAC

     a) Children that meet criteria 3.8.1a, c and d, have a bone age of less than 2.5 years and
        an annual growth velocity of greater than 8cm per year; or

     b) Commencement of GH is requested earlier than 12 months post renal transplant; or

     c) Applications to recommence GH following renal transplant if the GFR is above
        30 ml/minute/1.73 m2. Eligibility for reclassification under section 3.2 will be
        assessed.

3.8.3 Continuation criteria

Subsidised treatment can continue unless one or more of the following applies:

     a) The patient has reached skeletal maturity; and/or

     b) The patient’s height is equivalent to or above the 10th adult height centile; and/or

     c) The patient has failed to meet any of the response criteria listed at section 4.3.1 while
        on maximum dose for the last 6 month treatment period AND has failed to achieve
        and maintain mid parental height SDS12; and/or

     d) The decision is made to cease GH treatment. The following information should be
        provided in this instance:
                 Date of cessation;
                 Reason for cessation;
                 Final measurements at the time of cessation; and

11
  Growth velocity for bone age cannot be determined in children with a bone age of less than 2.5 years.
Children who meet criteria 3.8.1a, 3.8.1c and 3.8.1d, and have a bone age of less than 2.5 years, will be
approved for treatment if their annual growth velocity is equal to or less than 8cm per year.
12
  The treating doctor should inform the Department if there were any circumstances during the last treatment
period that may have impacted on the effectiveness of GH treatment. This will be taken into consideration when
assessing the patient’s response to treatment.

Guidelines for the PBS Growth Hormone Program                                                         15
                Quantity of GH supplies remaining at the patient’s delivery point.


3.9 Growth hormone deficiency and precocious puberty
3.9.1 Eligibility criteria

Patients may be eligible for growth hormone treatment irrespective of growth velocity and
height if all of the following criteria are met:
     a) Evidence of biochemical growth hormone deficiency; and

     b) A confirmed diagnosis of precocious puberty consistent with the definition in
        section 1; and

     c) Details of Gonadotrophin Releasing Hormone (GnRH) or other therapy should be
        provided (i.e. date of commencement and adequacy of pubertal suppression).

3.9.2 Exceptions when applications will be referred to the GHAC

     a) Nil.

3.9.3 Continuation criteria

Subsidised treatment can continue unless one or more of the following applies:

     a) The patient has reached skeletal maturity; and/or

     b) The patient has failed to meet any of the response criteria listed at section 4.3.1 while
        on maximum dose for the last 6 month treatment period AND has failed to achieve
        and maintain mid parental height SDS13; and/or

     c) The decision is made to cease GH treatment. The following information should be
        provided in this instance:

                Date of cessation;
                Reason for cessation;
                Final measurements at the time of cessation; and
                Quantity of GH supplies remaining at the patient’s delivery point.




13
  The treating doctor should inform the Department if there were any circumstances during the last treatment
period that may have impacted on the effectiveness of GH treatment. This will be taken into consideration when
assessing the patient’s response to treatment.

Guidelines for the PBS Growth Hormone Program                                                      16
3.10 Prader-Willi Syndrome
3.10.1 Eligibility criteria

All of the following criteria must be met in order to be eligible for GH treatment under the
category of Prader-Willi Syndrome:
     a) The patient is less than 18 years of chronological age; and

     b) PWS genetically proven and a copy of the laboratory result provided with the initial
        application; and

     c) Evaluated for airway obstruction and apnoea, including having had polysomnography
        (overnight sleep study), within 12 months of the date of application and any sleep
        disorder requiring treatment addressed; and

     d) The patient does not have uncontrolled morbid obesity14; and

     e) 6 months of recent growth data provided (at least two sets of data).

3.10.2 Exceptions when applications will be referred to the GHAC

     a) In the rare situation in which a patient has clinical criteria for PWS but no genetic
        abnormality can be detected by current means, consideration may be given to
        treatment after review by the GHAC, provided that there is written advice from a
        clinical geneticist.

3.10.3 Continuation criteria

Subsidised treatment can continue unless one or more of the following applies:

     a) The patient reaches 18 years of chronological age. A patient may continue to receive
        the balance of their current treatment period’s worth of approved treatment (usually six
        months) if they turn 18 during that treatment period; and/or

     b) The patient fails to meet at least one of the response criteria listed at section 4.3.2 at
        maximum dose for the last 6 month treatment period15; and/or

     d) The decision is made to cease GH treatment. The following information should be
        provided in this instance:

                Date of cessation;
                Reason for cessation;
                Final measurements at the time of cessation; and
                Quantity of GH supplies remaining at the patient’s delivery point.

If, in the patient’s most recent treatment period, the patient was receiving initial treatment for
the category of Prader-Willi Syndrome, the patient must also have had a sleep study test
performed during the initial treatment period

14
   Body weight greater than 200% of ideal body weight for height based on CDC 2000 data. Ideal body weight is
derived by calculating the 50th percentile weight for height.
15
   The treating doctor should inform the Department if there were any circumstances during the last treatment
period that may have impacted on the effectiveness of GH treatment. This will be taken into consideration when
assessing the patient’s response to treatment.

Guidelines for the PBS Growth Hormone Program                                                     17
Transitional arrangements for existing GH patients with PWS

   a) Doctors are encouraged to apply for the reclassification of PWS patients currently
      being treated with GH under sections 3.2 to 3.9. This is done by submitting an
      Application for initial supply of growth hormone for the treatment of Prader-Willi
      Syndrome form, which is available from the Department’s website at
      www.health.gov.au/hgh.




Guidelines for the PBS Growth Hormone Program                                     18
3.11 Exclusion criteria for initial and continuing treatment
3.11.1 All patients

The following patients (for all categories) are not eligible for GH treatment as a
pharmaceutical benefit:

     a) Children diagnosed with diabetes mellitus (except for the category of Biochemical
        Growth Hormone Deficiency) due to:

           the potential for growth hormone treatment to increase the risk of microvascular
            complications irrespective of whether the child is GH sufficient or deficient;
            and
           poor glycaemic control or other diabetes related issues may underlie the poor
            growth of patients who are GH sufficient; and

Note: GH treatment for patients with diabetes mellitus will only be considered for the
category of Biochemical Growth Hormone Deficiency in exceptional circumstances and only
in patients with proven biochemical growth hormone deficiency and after review by the
GHAC. Evidence of optimal glycaemic control, optimal nutrition (recent dietician
assessment), thyroid function and coeliac antibody screening as well as the results of baseline
complications screening should be provided.

     b) Children with a known risk of malignancy, including chromosomal abnormalities
        such as Down and Bloom Syndromes; and

     c) Where treatment with GH is assessed by the Department and/or the GHAC to be
        unsafe for a particular patient.

     d) Patients who have previously received treatment under the PBS GH program and
        who are applying for initial treatment16.

3.11.2 All patients excluding PWS patients

The following patients (excluding patients approved under section 3.10) are not eligible for
GH treatment as a pharmaceutical benefit:

     a) Patients with skeletal maturity; and

     b) Children with maturational or constitutional delay unless they have an estimated
        mature height (EMH) below the 1st centile.




16
   Patients who have previously received treatment under the PBS GH program and had that treatment ceased,
may only receive further GH treatment under the PBS GH program if they make an application to recommence
treatment. They cannot make another application for initial treatment.
Guidelines for the PBS Growth Hormone Program                                                   19
3.12 Recommencement criteria
     a) A patient who has had treatment ceased for failing to respond to GH while receiving
        maximum dose for a 6 month treatment period is not eligible to recommence GH
        treatment as a pharmaceutical benefit; unless the patient was suspended for one of the
        following reasons:

                The patient had a significant medical illness;
                The patient underwent major surgery (e.g. renal transplant);
                The patient had an adverse reaction to GH and after a period of observation the
                 treating doctor would like to recommence treatment; or
                Social/family problems had affected compliance.

     b) Applications to recommence subsidised GH treatment must include the following
        details:

                A letter from the treating doctor outlining why treatment was suspended and
                 the circumstances/reasons for recommencement;
                At least 6 months of recent growth data (as per the data required for an
                 application for continuing treatment) and a bone age reading taken within the
                 last 12 months;
                Assurance from the treating doctor that any compliance problems have been
                 addressed and the family are committed to continuing GH treatment.

     c) For recommencement applications that involve a change to the approved eligibility
        classification please refer to section 3.13.

     d) All recommencement applications are assessed by the Department. At its discretion,
        the Department may seek advice from the GHAC.17

3.13 Reclassification arrangements
     a) The treating medical practitioner may request a change to an existing patient’s
        approved eligibility classification at any 6 month application for continuing treatment,
        provided that adequate evidence is supplied to:

             a. show that the patient meets the eligibility criteria for initial treatment for the
                new category (described in sections 3.2 to 3.10.); or

             b. satisfy the Department that the patient would have met the eligibility criteria
                for initial treatment for the new category had the patient not previously
                received treatment with growth hormone

     b) The Department may seek the advice of the GHAC when assessing reclassification
        applications.

     c) At reclassification, the subsidised dose will be adjusted to the closest dose allowable
        for that classification.



17
  For patients seeking recommencement in a different category than for which they were previously approved,
who meet the eligibility criteria for initial treatment in the new category, the Department may choose to seek
advice from GHAC or a Departmental medical advisor on whether the proposed change of category is
appropriate for the person.
Guidelines for the PBS Growth Hormone Program                                                       20
4. DOSAGE
4.1 Dosing overview
      a) The requested GH brand, administration frequency and dose (in mg/m2/wk) must be
         included in each initial application and applications to continue treatment.

      b) Dosing schedules are produced by suppliers for each GH product. The Department
         encourages treating doctors to specify an absolute dose (mg/wk) at the time of
         application, that best aligns with the approved starting dose or the Dose Titration
         Chart.

      c) Unless specified otherwise by the treating doctor, the Department will select the
         closest available dose to the approved dose level (mg/m2/wk). For patients on the
         maximum dose, the dose selected by the Department will be within 3% of the
         maximum dose for the category of treatment.

      d) GH should be administered either 6 or 7 days per week by subcutaneous injection.

      e) PBAC endorsed doses for all indications are set out in the Dose Titration Chart below:

Dose Titration Chart – minimum to maximum subsidised doses

    Patients        SSG1                       TS2                   PWS                         PWS
    approved under: BGHD                       SHOX                  (non-mature                 (mature skeleton)3
                    CI                         CRI                   skeleton)3
                    H
                    PP
    Dose level 1    4.5mg/m2/wk                4.5 –                 4.5mg/m2/wk                 0.04mg/kg/wk
    Dose level 2    5.5mg/m2/wk                9.5mg/m2/wk           6mg/m2/wk
    Dose level 3    6.5mg/m2/wk                                      7.5mg/m2/wk
    Dose level 4    7.5mg/m2/wk
1
  An older child is eligible for any dose level at any time, provided that the treating practitioner requests the
higher dose.
2
 TS, SHOX and CRI patients may commence and/or continue GH at a dose of up to 9.5mg/m2/wk, if requested
by the treating doctor.
3
 Absolute dose for all PWS patients with a BMI > 85th centile for age will be calculated using ideal weight for
height.

Key to abbreviations of patient eligibility criteria
SSG     3.2 Short stature and slow growth
BGHD 3.3 Biochemical growth hormone deficiency
CI      3.4 Growth retardation secondary to an intracranial lesion or cranial irradiation
H       3.5 Neonates/infants at risk of hypoglycaemia secondary to growth hormone deficiency
TS      3.6 Turner Syndrome
SHOX 3.7 Short stature due to short stature homeobox (SHOX) gene disorders
CRI     3.8 Chronic renal insufficiency
PP      3.9 Growth hormone deficiency and precocious puberty
PWS     3.10 Prader-Willi Syndrome



Guidelines for the PBS Growth Hormone Program                                                            21
4.2 Starting dose
   a) Generally, dose level 1 will be approved for patients who have been approved for
      initial treatment, as indicated in the Dose Titration Chart.

   b) A higher starting dose may be approved for an older child up to the maximum dose,
      if requested by the treating doctor;

   c) A higher starting dose may be approved for a patient if:

           a. The higher dose is requested by the patient’s treating practitioner; and

           b. GHAC or a Departmental medical adviser considers there are exceptional
              circumstances that justify the higher dose; and

           c. The Department considers the higher dose is appropriate for the person after
              having regard to the advice from GHAC or the Departmental medical
              adviser.

4.3 Continuing dose
   a) Dose is reviewed by the Department at each 6 monthly application, at which time
      the treating doctor may request a change in dose. This timeframe allows new data
      to be gathered in order to demonstrate a patient’s response to treatment at the
      current subsidised dose, and to determine whether an increase of subsidised dose is
      warranted.

   b) Response to GH treatment is assessed based on the criteria in section 4.3.1 or 4.3.2.
      Demonstrated failure to meet one or more of the response criteria may result in an
      incremental dose increase as detailed in the Dose Titration Chart, up to the
      maximum dose (subject to meeting the continuation criteria at section 3.2 to 3.10).
      An increase in dose that is higher than the next dose level may be approved if:

           a. The higher dose is requested by the patient’s treating practitioner; and
           b. GHAC or a Departmental medical adviser considers there are exceptional
              circumstances that justify the higher dose; and
           c. The Department considers the higher dose is appropriate for the person after
              having regard to the advice from GHAC or the Departmental medical
              adviser.
   c) If all response criteria are met, the previous approved dose will be maintained,
      unless a higher dose is approved.
   d) In instances where there is an indication of serious non-compliance (eg stock
      running out earlier or lasting longer than expected), the Department will notify the
      treating doctor and will ask that an intervention plan be put in place to improve
      compliance with treatment.
   e) The absolute dose (mg/wk) is adjusted automatically at each 6 monthly application
      for any significant changes in BSA, to correspond to the dose level approved by the
      Department at the last application. Adjustment for BSA is undertaken for all
      patients, unless the treating doctor specifically requests otherwise.


Guidelines for the PBS Growth Hormone Program                                        22
     f) PWS patients who have just reached skeletal maturity will require phased dose
        readjustment and titration to 0.04mg/kg/wk, which will be based on the advice of
        the GHAC. As a result, response or non-response may take a longer period to
        become evident. This factor should be considered during the first reapplication after
        reaching skeletal maturity.

4.3.1 Response criteria for all patients excluding Prader-Willi Syndrome

Patient response to GH will be measured against the following criteria:

     a) achievement of 50th percentile growth velocity for bone age; and
     b) increase in height SDS for chronological age; and
     c) a minimum growth velocity of 4cm/year.

4.3.2 Response criteria for Prader-Willi Syndrome patients

Patient response to GH will be measured against the following criteria:

a)    Non-mature skeleton                   b)    Non-mature skeleton                      c) Mature skeleton
       Less than maximum dose for                  Maximum dose for last
       last treatment period                       treatment period
    improving height centile (CDC              maintaining or improving height              maintaining or
     2000); and                                  centile (CDC 2000); and                       improving BMI or BMI
                                                                                               SDS (CDC 2000); and
    improving BMI SDS (CDC                     maintaining or improving BMI
     2000); and                                  SDS (CDC 2000); and                          maintaining or
                                                                                               improving waist
    improving waist circumference              maintaining or improving waist
                                                                                               circumference or waist
     (SDS and/or waist/height ratio);            circumference (SDS or
                                                                                               circumference SDS or
     and                                         waist/height ratio); and
                                                                                               waist/height ratio; and
    crossing height centiles                   crossing height centiles upwardly
                                                                                              maintaining or
     upwardly on untreated PWS                   on untreated PWS standards
                                                                                               improving weight SDS
     standards (Butler et al); and               (Butler et al); and
                                                                                               (CDC 2000); and
    improving age standardised                 maintaining * or improving age               maintaining * or
     measures of body composition                standardised measures of body                 improving standardised
     using dual energy X-ray                     composition. ^                                measures of body
     absorptiometry or bioelectrical
                                                                                               composition. ^
     impedance. ^
^ The treating doctor must provide the specific data on which they have judged this improvement.
* Maintenance of a response is defined as a value within a 5% tolerance (this allows for seasonal and other
measurement variations).

4.3.3 Evaluation of response to treatment and corresponding dose for Prader-Willi
       Syndrome patients
Please see Attachment 6.4, Evaluation of response to treatment and corresponding dose for
PWS patients, for details of how response to treatment is evaluated and the corresponding
dose.




Guidelines for the PBS Growth Hormone Program                                                        23
5. ADMINISTRATIVE ARRANGEMENTS
5.1 Initial treatment
   a) Applications to commence GH treatment will be assessed by the Department based
      on the eligibility criteria outlined in the National Health (Growth Hormone
      Program) Special Arrangement 2011 (PB 88 of 2011), as reflected in section 3 of
      these Guidelines.

   b) Applications for GH must be signed and submitted by a specialist paediatrician or a
      specialist paediatric endocrinologist with the provision of their prescriber number.

   c) A covering letter providing details of the patient’s medical history must be
      submitted with all new applications, including:

                  Relevant medical history;
                  Relevant social history;
                  Relevant investigations; and
                  Concurrent medication.

   d) In all cases an Application for initial supply of growth hormone or Application for
      initial supply of growth hormone for the treatment of Prader-Willi Syndrome form
      must be completed and all requested information provided. This includes the
      provision of signed consent by the parent/guardian of the child for data to be
      provided to the Department to enable an assessment of initial and continuing
      eligibility for treatment.

   e) The Department will not consider an application until all necessary information is
      submitted.

   f) At the time of submission, the most recent height and weight data must be no more
      than 3 months old. The requested GH brand, administration frequency and dose
      (mg/m2/wk) must also be addressed at the time of application.

   g) Patients will only be supplied with products that have marketing approval for the
      treatment of their condition. See Attachment 6.3 for further details.

   h) The Department will inform the treating medical practitioner in writing of the
      outcome of the application for subsidised GH.

   i) If the application is approved, approximately 32 weeks of treatment will be initially
      supplied (made up of an initial supply of 19 weeks and a balance supply of 13
      weeks). This incorporates approximately 6 weeks of additional supply beyond that
      provided at each subsequent reapplication. The purpose of this additional supply is
      to allow the patient’s family and the treating doctor to establish an appropriate
      review regimen so that future reapplications may be lodged on time with all
      required data.




Guidelines for the PBS Growth Hormone Program                                        24
5.2 Continuing treatment
   a) All patients approved to receive subsidised GH treatment must be assessed for their
      response to treatment every 6 months.

   b) Applications to continue GH treatment are assessed by the Department according to
      the response criteria outlined in the National Health (Growth Hormone Program)
      Special Arrangement 2011 (PB 88 of 2011), as reflected in section 4.3.1 and
      section 4.3.2.

   c) Applications to continue treatment must be submitted approximately 4 weeks
      before current supplies are due to run out, using the Application for continued
      supply of growth hormone form or the Application for continued supply of growth
      hormone for the treatment of Prader-Willi Syndrome form, and ensuring that all
      required data is provided.

   d) All applications for continuing treatment must be signed and submitted by a
      specialist paediatrician, specialist paediatric endocrinologist or a registered medical
      practitioner in consultation with a specialist paediatrician or a specialist paediatric
      endocrinologist. If there is a change of practitioner, the new practitioner’s
      prescriber number must be provided.

   e) Each approval for continuing GH treatment covers a 6 month treatment period.
      Supplies of GH product are ordered from the supplier in two batches: an initial
      13 week supply followed by a 13 week automatic ‘balance’ supply.

   f) A letter is sent to the treating medical practitioner following the assessment of each
      6 monthly reapplication. If approved for continuing treatment, the letter includes
      important information such as the approved subsidised dose for the next 6 months,
      the date on which the new supply should be commenced by the patient, and the date
      that supply is expected to finish by.

   g) It is the responsibility of the treating medical practitioner to inform the patient
      and/or the patient’s parent(s)/guardian(s) of each new approved dose, the frequency
      of administration and when the new supply should be started.

5.3 Supply of growth hormone




Guidelines for the PBS Growth Hormone Program                                         25
5.4 Dispensing of growth hormone
   a) Each new applicant must nominate a community or hospital pharmacy, or a
      medical practitioner approved to supply pharmaceutical benefits under section 92
      of the National Health Act 1953, for the delivery and dispensing of growth
      hormone, including confirmation that the nominated dispenser has agreed to
      receive and dispense growth hormone on behalf of the patient.

   b) The treating medical practitioner must notify the Department if the patient moves
      or changes their nominated dispenser.

   c) The Poisons Standard 2009 (prepared under the Therapeutic Goods Act 1989)
      specifies that growth hormone is a Schedule 4 drug (prescription only medicine).
      Accordingly, the patient must present the pharmacist with a legal prescription from
      their treating doctor in order to collect growth hormone supplies.

   d) The Department will send a letter to the dispenser confirming the drug and strength,
      dose, and frequency that has been approved by the Department for that patient.

   e) No Government co-payment applies to growth hormone under Section 100 of the
      National Health Act 1953.

   f) Dispensers do not need to complete a Section 100 reimbursement application, as
      growth hormone is purchased by the Department directly.

   g) Nominated dispensers must review the documentation provided by the
      supplier/courier upon receipt of delivery of growth hormone, including verifying
      the total number of vials received, brand, strength, expiry date and H number
      against the details specified. The form should be signed and promptly faxed back to
      the supplier.

5.5 Patients travelling overseas
   a) The supply of subsidised growth hormone to patients travelling overseas will be
      subject to the following conditions:

          (i)   A maximum quantity of six months of growth hormone may be authorised and
                supplied to the patient prior to departure.

          (ii) Further supplies of growth hormone will only be ordered on receipt of an
               application for continued treatment. Applications must be submitted every six
               months by an Australian medical practitioner, in consultation with a
               paediatrician or paediatric endocrinologist.

          (iii) Supplies will only be delivered to a community or hospital pharmacy in
                Australia.

          (iv) The patient must continue to meet the residency requirements defined in
               Section 3.1a, as verified by a patient’s Medicare card details.




Guidelines for the PBS Growth Hormone Program                                      26
   b) If you are planning to take PBS medicines overseas for your own personal use or
      the personal use of someone travelling from Australia with you (for example a
      child), it is recommended that you:

          (i)   contact the embassy of the country you are visiting, as well as any transit
                countries, to ensure the medicine is legal there and identify any import/export
                restrictions;

          (ii) carry or enclose a letter/prescription from your doctor detailing what the
               medicine is, how much you will be taking and stating that the medicine is for
               your personal use;

          (iii) leave the medicine in its original packaging with dispensing labels attached and
                carry in your hand luggage; and

          (iv) Note that medicines brought into and taken out of Australia may be subject to
               import and export controls. Further information is available at:
               http://www.health.gov.au/internet/main/publishing.nsf/Content/general-
               guidance-for-travellers-bringing-medicines-to-and-from-australia

5.6 Compliance with the administration of growth hormone treatment
   a) The treating medical practitioner must advise the parent/guardian of the patient of
      the correct storage conditions for the product in order to maintain its potency (refer
      to Attachment 6.2).

   b) The treating medical practitioner is encouraged to contact the patient’s
      family/guardian promptly after each approval for continuing treatment to advise of
      the new approved dose, injection frequency and the commencement date for the
      next supply of GH and provide a corresponding prescription. This will help to
      avoid dosing errors being made by the patient.

   c) At each application for continued treatment the treating medical practitioner must
      provide details of the amount of GH the patient has remaining. This allows the
      Department to determine an accurate commencement date of the next treatment
      period and to manage the timing of new supply arrangements for the patient. This
      also helps to identify if the patient has been compliant with treatment.

   d) If the patient’s remaining supply of GH has run out more than 3 weeks before or
      3 weeks after the date supply was expected to finish by, the treating medical
      practitioner is requested to explore the circumstances surrounding this occurrence
      and provide information to the Department.

   e) If the patient encounters difficulty administering the GH product or using the GH
      pen device, further assistance can be sought from a nurse educator recommended
      by the treating medical practitioner.

   f) Annual measurement of IGF-1 is recommended to monitor responsiveness to
      and/or compliance with treatment.

   g) If a patient demonstrates recurring compliance problems the Department will
      request that the treating medical practitioner take measures to investigate and
      improve the situation as far as practicable. If compliance problems continue, the
      Department may consider ceasing subsidised GH treatment.

Guidelines for the PBS Growth Hormone Program                                         27
   h) The Department encourages the reporting of all adverse drug reactions thought to
      be attributable to treatment with GH. These should be reported to the Advisory
      Committee on the Safety of Medicines of the Therapeutic Goods Administration
      (TGA). Reports of suspected adverse drug reactions can be made by using a
      prepaid reporting form (“Blue Card”) which is available from the TGA’s website:
      www.tga.gov.au/adr/bluecard.htm.

       Completed Blue Cards can be sent to the TGA:
              By mail to: Medicines Safety Monitoring, Reply Paid 100, WODEN ACT
               2606
              By fax to: 02 6203 1616
              By email to: adr.reports@tga.gov.au
              Report electronically at
               www.ebs.tga.gov.au/ebs/ADRS/ADRSRepo.nsf?OpenDatabase

   i) Information on adverse drug reactions should also be provided to the Department.

   j) The treating medical practitioner should inform the Department as soon as possible
      if the patient stops GH treatment. Unused supplies which have been taken home by
      the patient should be returned to a local pharmacy for correct disposal.

5.7 OZGROW
   a) The Australian paediatric growth hormone database ‘OZGROW’ collates data on
      all patients receiving GH, which is used for research into and evaluation of growth
      hormone use.

   b) As part of the process of applying to commence GH treatment, informed consent is
      obtained from the patient’s parent /guardian for specific information to be supplied
      to the PBS Growth Hormone Program and transferred to OZGROW on a regular
      basis. Details of the type of patient data that is transferred to OZGROW can be
      found on the back page of the Application for initial supply of growth hormone
      form.

   c) The data transferred to OZGROW is de-identified and allocated an OZGROW non-
      identifiable patient number in order to maintain patient confidentiality.

5.8 Review of decisions
   a) Decisions may be reviewed by the GH Program Director’s manager (the Delegate).
      In reviewing the original decision, and any new information provided, the Delegate
      may also seek the advice of the GHAC and/or the GH Program’s Medical Advisor.
      The treating medical practitioner will be advised of the outcome of the review by
      the Delegate.

   b) Treatment decisions that can be reviewed include:

              initial application not approved by the Department;
              continuing treatment not approved by the Department;
              reclassification application not approved by the Department; or
              recommencing application not approved by the Department.


Guidelines for the PBS Growth Hormone Program                                      28
   c) Dosage has been considered and recommended by the Pharmaceutical Benefits
      Advisory Committee (PBAC). The Department administers dose in accordance
      with PBAC advice. Dose appeals may be reviewed by the Department based on the
      individual merits of the case.

   d) A request for review cannot be made prior to a decision being made by the
      Department. Initial applications that contain a request to refer the case to the
      GHAC for advice will not automatically be done so, unless it is deemed necessary
      by the Department.

   e) A request for review must be lodged in writing with the Department within 6
      months of the date of the Department’s original decision as notified to the treating
      medical practitioner in writing.

   f) The medical practitioner must provide additional information to support the claim
      that the Department’s original decision should be reviewed. This should include a
      clear statement outlining the reasons the physician believes the patient should be
      considered eligible for treatment.

5.9 Role of the Growth Hormone Advisory Committee
   a) The role and functions of the Growth Hormone Advisory Committee (GHAC) are
      outlined in Terms of Reference available from the Department’s website at
      www.health.gov.au/hgh

   b) The purpose of the GHAC is to provide assistance to the Department of Health and
      Ageing in its administration of the Pharmaceutical Benefits Scheme (PBS) Growth
      Hormone Program. This includes providing clinical and where possible evidence-
      based advice in cases that do not clearly meet the eligibility criteria for
      commencing or continuing growth hormone treatment, as specified in these
      Guidelines.

   c) Applications are sent by the Department to three GHAC members for out of session
      review (one being the Chairperson). The Chairperson provides the final
      recommendation to the Department taking into account the other members’
      assessments.

   d) The five members of the GHAC meet every second month by telephone conference
      to discuss and make recommendations to the Department, where consensus cannot
      be reached by out of session review or where the case is particularly complex.

   e) Members of the GHAC must not provide advice on patients under their own care or
      where another conflict of interest is apparent.

   f) Members seek the cooperation of treating physicians in providing as much detailed
      information as possible including precise diagnosis, other drug therapy and social
      and medical issues that may affect response to treatment. This information will be
      taken into consideration by the Department and/or the GHAC when assessing
      eligibility for treatment.




Guidelines for the PBS Growth Hormone Program                                       29
5.10 Departmental details
Contact details for submission of applications and all enquiries are as follows:
   PBS Growth Hormone Program                          Phone:      (02) 6289 7274
   Pharmaceutical Programs and Support Branch          Fax:        (02) 6289 3175
   Pharmaceutical Benefits Division
   Department of Health and Ageing                     Email:      hgh@health.gov.au
   MDP 953                                             Web:        www.health.gov.au/hgh
   GPO Box 9848
   CANBERRA ACT 2601




Guidelines for the PBS Growth Hormone Program                                       30
6.     ATTACHMENTS
6.1 Growth hormone preparations available as a Pharmaceutical Benefit
This information is also available at www.pbs.gov.au.
Somatropin - (recombinant Growth Hormone)
Please note that 1mg of growth hormone is equivalent to 3 iu.
Note: Some restrictions may apply to the brands that can be prescribed for certain eligibility categories. See
attachment 6.3 for more details.

Genotropin®                   5mg       in 1ml multi-use two-compartment cartridge (with preservative)
(Pfizer Australia Pty         12mg      in 1ml multi-use two-compartment cartridge (with preservative)
Limited)
Genotropin GoQuick®           5mg       in 1ml pre-filled two-compartment cartridge (with preservative)
(Pfizer Australia Pty         12mg      in 1ml pre-filled two-compartment cartridge (with preservative)
Limited)*
Genotropin MiniQuick®         Available in boxes of 7 prefilled syringes
(Pfizer Australia Pty
Limited)                      0.6mg     in 1ml multi-use two-compartment cartridge (No preservative)
                              0.8mg     in 1ml multi-use two-compartment cartridge (No preservative)
                              1mg       in 1ml multi-use two-compartment cartridge (No preservative
                              1.2mg     in 1ml multi-use two-compartment cartridge (No preservative)
                              1.4mg     in 1ml multi-use two-compartment cartridge (No preservative)
                              1.6mg     in 1ml multi-use two-compartment cartridge (No preservative)
                              1.8mg     in 1ml multi-use two-compartment cartridge (No preservative)
                              2mg       in 1ml multi-use two-compartment cartridge (No preservative)

Humatrope                    6 mg      multi-use cartridge with 3.15ml diluent syringe (with preservative)
(Eli Lilly Australia Pty      12mg      multi-use cartridge with 3.15ml diluent syringe (with preservative)
Limited)                      24mg      multi-use cartridge with 3.15ml diluent syringe (with preservative)
Norditropin® SimpleXx        5mg       5mg/1.5mL multi-use cartridge (with preservative)
(Novo Nordisk                 10mg      10mg/1.5mL multi-use cartridge (with preservative)
Pharmaceuticals Pty Ltd)      15mg      15mg/1.5mL multi-use cartridge (with preservative)

Norditropin NordiFlex®        5mg        5mg/1.5mL multi-dose pre-filled pen (with preservative)
(Novo Nordisk                 10mg      10mg/1.5mL multi-dose pre-filled pen (with preservative)
Pharmaceuticals Pty Ltd)      15mg      15mg/1.5mL multi-dose pre-filled pen (with preservative)

Norditropin FlexPro®          5mg        5mg/1.5mL multi-dose pre-filled pen (with preservative)
(Novo Nordisk                 10mg      10mg/1.5mL multi-dose pre-filled pen (with preservative)
Pharmaceuticals Pty Ltd)      15mg      15mg/1.5mL multi-dose pre-filled pen (with preservative)

Nutropin Aq®                  10mg      10mg/2.0ml multi-use cartridge (with preservative)
(Ipsen Pty Ltd)

Omnitrope®                    5 mg      solution for injection 5mg (15iu) in 1.5mL cartridge (with preservative)
(Sandoz Pty Ltd)              10mg      solution for injection 10mg (30iu) in 1.5mL cartridge (with preservative)

Saizen Click.Easy            8mg        vial with 1.37 mL diluent cartridge (with preservative)
(Merck Serono Pty Ltd)                   for use with one.click auto-injection.

Saizen EasyPod®               6mg        solution for injection 6mg (18 i.u.) in 1.03 mL cartridge (with preservative)
(Merck Serono Pty Ltd)        12mg       solution for injection 12mg (36 i.u.) in 1.5 mL cartridge (with preservative)
                              20mg       solution for injection 20mg (60 i.u.) in 2.5 mL cartridge (with preservative)
Zomacton                     4mg        vial with diluent (with preservative)
(Ferring Pharmaceuticals      10mg       vial with diluent (with preservative)
Pty Ltd)



Guidelines for the PBS Growth Hormone Program                                                          31
  6.2 Storage of Growth Hormone

  Growth hormone should NOT be frozen, heated or exposed to direct light. Exposure to light
  and temperatures outside those noted in the table below will adversely affect the potency of
  the growth hormone.

Product                                               Storage                      Shelf Life
                                                    Temperature
                                                                         Single dose only. Following
                                                                     reconstitution, the injection should be
Genotropin MiniQuick® 0.6mg cartridge*                 2-25°C
                                                                     used immediately but can be stored at
                                                                           2-8°C for up to 24 hours.
Genotropin MiniQuick® 0.8mg cartridge*                 2-25°C                       As above
Genotropin MiniQuick® 1.0mg cartridge*                 2-25°C                       As above
Genotropin MiniQuick® 1.2mg cartridge*                 2-25°C                       As above
Genotropin MiniQuick® 1.4mg cartridge*                 2-25°C                       As above
Genotropin MiniQuick® 1.6mg cartridge*                 2-25°C                       As above
Genotropin MiniQuick® 1.8mg cartridge*                 2-25°C                       As above
Genotropin MiniQuick® 2.0mg cartridge*                 2-25°C                       As above

Genotropin® 5.0mg cartridge                             2-8°C                       28 Days
Genotropin® 12.0mg cartridge                            2-8°C                       28 Days

Genotropin GoQuick® 5.0mg in 1ml pre-filled two
                                                        2-8°C                       28 Days
compartment cartridge (with preservative)#
Genotropin GoQuick® 12.0mg in 1ml pre-filled two
                                                        2-8°C                       28 Days
compartment cartridge (with preservative) #
Humatrope® 6.0mg cartridge                              2-8°C                       28 Days
Humatrope® 12.0mg cartridge                             2-8°C                       28 Days
Humatrope® 24.0mg cartridge                             2-8°C                       28 Days

Norditropin SimpleXx® 5.0mg cartridge                   2-8°C                       28 Days
Norditropin SimpleXx® 10.0mg cartridges                 2-8°C                       28 Days
Norditropin SimpleXx® 15.0mg cartridges                 2-8°C                       28 Days

Norditropin NordiFlex® 5.0mg pre-filled pen             2-8°C                       28 Days
Norditropin NordiFlex® 10.0mg pre-filled pen            2-8°C                       28 Days
Norditropin NordiFlex® 15.0mg pre-filled pen            2-8°C                       28 Days

Norditropin FlexPro® 5.0mg pre-filled pen               2-8oC                       28 Days
Norditropin FlexPro® 10.0mg pre-filled pen              2-8oC                       28 Days
Norditropin FlexPro® 15.0mg pre-filled pen              2-8oC                       28 Days

Nutropin Aq® 10.0mg cartridge                           2-8°C                       28 Days

Omnitrope® 5.0mg cartridge                              2-8°C                       21 Days
Omnitrope® 10.0mg cartridge                             2-8°C                       28 Days

Saizen click.easy® 8.0mg cartridge^                    2-25°C                       28 Days
Saizen easypod® 6.0 mg vial                             2-8°C                       28 Days
Saizen easypod® 12.0 mg vial                            2-8°C                       28 Days
Saizen easypod® 20.0 mg vial                            2-8°C                       28 Days

Zomacton® 4.0mg cartridge                               2-8°C                       14 Days
Zomacton® 10.0mg cartridge                              2-8°C                       14 Days
  *Genotropin MiniQuick products are preservative free. After reconstitution, Genotropin MiniQuick
  products should be stored at 2-8°C.
  ^After reconstitution, Saizen click.easy 8.0mg must be stored at 2-8°C.

  Guidelines for the PBS Growth Hormone Program                                                 32
6.3       Brand prescribing restrictions based on approved eligibility category

This attachment is effective from 1 September 2010.

Products approved for marketing for use by patients with chronic renal insufficiency:

Genotropin® range of products
Humatrope range of products (pre-pubertal18 children only)
Norditropin® range of products
Nutropin Aq®
Omnitrope® - only for children above 3 years of age


Products approved for marketing for use by patients with Prader-Willi Syndrome:

Genotropin® range of products



Products approved for marketing for use by all other patient eligibility categories:

All growth hormone products subsidised through the PBS Growth Hormone Program are
available for the remaining patient categories.

Please note: Omnitrope® is indicated for the treatment of children above three years of age.




18
     height < 25th percentile and growth velocity less than or equal to 25 th percentile for bone age
Guidelines for the PBS Growth Hormone Program                                                           33
     6.4      Evaluation of response to treatment and corresponding dose for PWS patients
      Last 6 months               Response                                 BMI                              Outcome                                                                                                    Tick
      Non-mature                  All response criteria are met.           < 85th centile for age           Maintain previous approved dose (adjusted for BSA).
      skeleton –                                                           > 85th centile for age           Maintain previous approved dose (adjusted for BSA).
      not on max dose                                                                                       IBW for height: _____kg
                                                                                                            BSA: √ (height_____cm x IBW_____kg)/3600 = _____m2
                                                                                                            ____/m2/wk x _____m2 = _____mg/wk
                                                                                                            Comments:
                                  Patient does not meet all of             < 85th centile for age           Increase dose incrementally by 1.5mg/m2 /wk (may not exceed 7.5mg/m2/wk).
                                  the response criteria.
                                                                           > 85th centile for age           Increase dose incrementally by 1.5mg/m2 /wk.
                                                                                                            IBW for height: _____kg
                                                                                                            BSA: √ (height_____cm x IBW_____kg)/3600 = _____m2
                                                                                                            ____/m2/wk x _____m2 = _____mg/wk
                                                                                                            Comments:
                                  Response to Rx is unclear.               N/A                              Refer to GHAC for advice.
      Non-mature                  Patient meets at least one of            < 85th centile for age           Continue treatment at maximum dose (adjusted for BSA).
      skeleton –                  the response criteria.                   > 85th centile for age           Continue treatment at maximum dose (adjusted for BSA).
      on max dose                                                                                           IBW for height: _____kg
                                                                                                            BSA: √ (height_____cm x IBW_____kg)/3600 = _____m2
                                                                                                            7.5/m2/wk x _____m2 = _____mg/wk
                                                                                                            Comments:
                                  Patient does not meet any of             N/A                              No longer eligible to receive GH treatment. CEASE TREATMENT.
                                  the response criteria.
      Mature skeleton             The patient meets at least one           < 85th centile for age           Eligible to receive GH treatment for the next 6 months at 0.04mg/kg/week.
      >=13.5 yrs (female)         of the response criteria.                                                 0.04mg x current weight______kg = _____mg/wk
      >=15.5 yrs (Male)
                                                                                                            Comments:
                                                                            > 85th centile for age          Eligible to receive GH treatment for the next 6 months at 0.04mg/kg/week.
                                                                                                            IBW for height: _____kg                0.04mg x IBW______kg = _____mg/wk
                                                                                                            Comments:
                                  Patient does not meet any of                                              No longer eligible to receive GH treatment. CEASE TREATMENT.
                                  the response criteria.
      *Note: If a patient has reached skeletal maturity during the last 6 month treatment period, assess their response to treatment based on the dose approved at the last reapplication. If they are eligible to continue
      treatment, the dose will need to be titrated to the skeletal maturity dose (0.04mg/kg/week). Referral to GHAC may be required to seek advice regarding dose titration.



Guidelines for the PBS Growth Hormone Program                                                                    34

								
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