AETNA BETTER HEALTH OF PENNSYLVANIA
Clinical Practice Guideline
PHARMACY PRIOR AUTHORIZATION
Clinical Guideline - Growth Hormone and related agents
Genotropin®, Humatrope®, Norditropin®, Nutropin®, Omnitrope®,
Saizen®, Serostim®, Tev-Tropin®, Valtropin®, Zorbtive® (somatropin),
Egrifta® (tesamorelin), Increlex®, Iplex® (mecasermin), Somavert® (pegvisomant)
Indications:
 Genotropin
o Growth Hormone Deficiency (Pediatric and Adult populations)
o Growth failure associated with Prader-Willi Syndrome
o Short stature born SGA with no catch-up growth by 2 to 4 years of age (>2 yrs old)
o Growth failure associated with associated with Turner Syndrome
o Idiopathic Short Stature (Pediatric population -NOT MEDICALLY NECESSARY FOR THIS
INDICATION)
 Humatrope
o Growth Hormone Deficiency (Pediatric and Adult populations)
o Short stature born SGA with no catch-up growth by 2 to 4 years of age (>2 yrs old)
o Growth failure associated with associated with Turner Syndrome
o Idiopathic Short Stature (Pediatric population -NOT MEDICALLY NECESSARY FOR THIS
INDICATION)
o Short stature homeobox–containing gene deficiency (SHOX deficiency - Pediatric
population)
 Norditropin
o Growth Hormone Deficiency (Pediatric and Adult populations)
o Short stature born SGA with no catch-up growth by 2 to 4 years of age (>2 yrs old)
o Growth failure associated with associated with Turner Syndrome
o Growth failure associated with Noonan syndrome
 Nutropin, (Nutropin AQ, Nutropin AQ NuSpin)
o Growth Hormone Deficiency (Pediatric and Adult populations)
o Short stature born SGA with no catch-up growth by 2 to 4 years of age (>2 yrs old)
o Idiopathic Short Stature (Pediatric population -NOT MEDICALLY NECESSARY FOR THIS
INDICATION)
o Growth failure associated with chronic renal insufficiency
 Omnitrope, Saizen
o Growth Hormone Deficiency (Pediatric and Adult populations)
 Tev-Tropin
o Growth Hormone Deficiency (Pediatric populations)
o Growth failure associated with Prader-Willi Syndrome
 Valtropin
o Growth Hormone Deficiency (Pediatric and Adult populations)
o Growth failure associated with associated with Turner Syndrome
 Iplex, Increlex (Limited Access)
o IGF-1 deficiency
1
Last Review: 01/2013
PARP Approval 05/2013
AETNA BETTER HEALTH OF PENNSYLVANIA
Clinical Practice Guideline




Serostim
o HIV-associated failure to thrive in children (off-label use)
o AIDS-associated wasting syndrome, or cachexia in adults
Zorbtive
o Short-bowel syndrome in adult patients receiving specialized nutritional support
Egrifta
o For treatment of excess abdominal fat in HIV-infected patients with lipodystrophy
Somavert
o For the treatment of acromegaly in patients who have had an inadequate response to
surgery and/or radiation therapy and/or other medical therapies, or for whom these
therapies are not appropriate
Authorization Guidelines:
For Patients who meet all of the following:
 Not used for idiopathic short stature (considered cosmetic use and not medically necessary)
 No evidence of diabetic retinopathy (proliferative and non proliferative) per medical records
 No evidence of active malignant conditions per medical records
 No evidence of acute critical illness per medical records
 No hypersensitivity to any of the product components.
 No hypersensitivity to benzyl alcohol (Nutropin, Omnitrope, Saizen, Serostim, Tev-Tropin, Zorbtive
diluent only)
 No sensitivity to glycerin or M-cresol (Humatrope diluent)
 Not used for growth promotion in pediatric patients with epiphyseal closure (linear growth can no
longer occur. i.e., bone age>14 yrs old) The potential for achieving additional growth after Tanner
4-5 (full maturity) is small as this correlates with epiphyeseal closure.
Growth Hormone Deficiency (GHD) - Neonates/Infants:
 Random GH level <20ng/ml (by RIA test).
 Abnormal IGFBP-3 (in infants)
 Other causes have been ruled out or treated (hypothyroidism, metabolic disorders)
Initial Approval:
 Pediatric Growth Failure Indications: 6 months (document baseline information)
 Pediatric HIV-associated failure to thrive (Serostim): 3 months (document baseline height,
weight, IBW, usual weight)
 Adult GHD: 6 months (document baseline IGF-I, GH test results, dose)
 Adults with wasting due to HIV or AIDS (Serostim): 3 months (document height, weight, IBW,
usual weight)
 Adults with SBS (Zorbtive): one four-week course of therapy
 Adults with excess abdominal fat in HIV-infected patients with lipodystrophy (Egrifta): 3
months
 Adults with Acromegaly (Somavert): 6 months
2
Last Review: 01/2013
PARP Approval 05/2013
AETNA BETTER HEALTH OF PENNSYLVANIA
Clinical Practice Guideline
Renewal
Pediatric Growth Failure Indications - Continue 6 month renewals if:
 Final height has not been achieved
 Epiphyses are open, so linear growth is possible
 Growth velocity is >5cm/year on current dose, or growth velocity is <5cm/year but dose has
been increased or member is reaching final appropriate height.
Note: Growth velocity will typically decrease as final height is approached (growth velocity <2
cm/year).
 Review of the pharmacy claims history supports compliance
Pediatric HIV-associated failure to thrive (Serostim) - Reauthorize for 12 weeks (maximum 48 weeks
total) if:
 Documentation supports clinical response and weight gain
Adults with GHD Reauthorize for 1 year if:
 Dose has been adjusted to target serum IGF-1 at the middle for the age-and sex-appropriate
reference range quoted by the laboratory used
Reauthorize for 6 months if:
 IGF-I is low but dose is being increased
Adults with wasting due to HIV or AIDS (Serostim) - Reauthorize for 12 weeks (maximum 48 weeks
total) if:
 Documentation supports clinical response and weight gain
Adults with excess abdominal fat in HIV-infected patients with lipodystrophy (Egrifta) - Reauthorize
for 3 months if:
 Documentation supports clinical response
Adults with Acromegaly (Somavert) - Indefinite authorization if:
 Documentation supports normal IGF-1 levels
3
Last Review: 01/2013
PARP Approval 05/2013
AETNA BETTER HEALTH OF PENNSYLVANIA
Clinical Practice Guideline
Pediatrics Diagnosis
Required documentation
GHD
 Recent (within the last 3 months) height and weight and pretreatment growth velocity
(Note: most patients will have short stature: height <5th percentile for age and sex)
 Other factors contributing to growth failure have been ruled out, or are being treated
(e.g., hypothyroidism – normal TSH, T4)
 For members ≥Tanner Stage 3 or, ≥ 14 years old - Recent bone age to support open
epiphyses so linear growth can occur (i.e., bone age <14 years of age) was optional
before
 Fasting Growth Hormone Stimulation test with arginine, clonidine, glucagon, insulin or
levodopa: Peak <10 ng/ml (by RIA), or Peak <5 ng/ml (by IRMA)
 1 agent with peak level required if cause is known:
o Structural or developmental abnormalities: anencephaly, pituitary
aplasia
o Genetic disorders: e.g., PROP1 and PIT1 mutations, septo-optic dysplasia
o Acquired causes: e.g., craniopharyngeomas*, cranial irradiation, brain
surgery, head trauma, CNS infections
 2 agents with peak levels required if cause is unknown (idiopathic).
 Documentation to support the diagnosis (e.g., Turner Syndrome confirmed by
karyotype studies)
 Recent (within the last 3 months)
 height <5th percentile of the normal growth curve for age and sex,
 weight, and
 pretreatment growth velocity
 For members ≥Tanner Stage 3 or, ≥ 14 years old; Recent bone age to support open
epiphyses so linear growth can occur (i.e., bone age <14 years of age)
 Documentation to support the diagnosis of CRI prior to renal transplant
 Documentation to support correction of existing metabolic abnormalities
 For members ≥ Tanner Stage 3 or, ≥ 14 years old
 Recent height and weight (within the last 3 months) and pretreatment growth
velocity (Note: patients may not have short stature)
 At least 2 years of age
 Documented
 Birth weight or length <3rd percentile for gestational age, or
 Birth weight <2500 grams at a gestational age of more than 37 weeks
If GHD is attributed to an
intracranial tumor, absence of
tumor growth or recurrence
should be documented for 6-12
months before initiation of GH.
Note – In 2009, FDA has
restricted use of Iplex to current
patients receiving therapy. Iplex
is unavailable for new patients.
Turner Syndrome (TS),
Prader-Willi Syndrome,
SHOX deficiency, or Noonan
Syndrome
Chronic Renal Insufficiency
(CRI)
Small for Gestational Age
(SGA) with failure to catchup by
2-4 years of age
IGF-1 Deficiency
(Increlex only)
 Recent (within the last 3 months)
 height <5th percentile of the normal growth curve for age,
 weight, and
 pretreatment growth velocity
 For members ≥Tanner Stage 3 or, ≥ 14 years old; Recent bone age to support open
epiphyses so linear growth can occur (i.e., bone age <14 years of age)
 ≥ 2 years of age (Increlex),
 No evidence of epiphyseal closure
 No hypersensitivity to mecasermin or benzyl alcohol (Increlex only)
 No evidence of neoplastic disease
 Documentation supports a diagnosis of IGF-1 deficiency (other causes of low IGF-1
have been ruled out)
 height standard deviation score less than or equal to −3
4
Last Review: 01/2013
PARP Approval 05/2013
AETNA BETTER HEALTH OF PENNSYLVANIA
Clinical Practice Guideline
Pediatric patients: HIVassociated failure to thrive
(Serostim): (off label)




basal IGF-1 standard deviation score less than or equal to −3
normal or elevated growth hormone levels
Height, weight, IBW, usual weight
Progressive weight loss below IBW (or usual body weight if usual weight <IBW) over
the last year
 Dietary consult and dietary modifications over the past 3 months with documented
adequate caloric intake
 Metabolic panel to r/o volume depletion- look for a BUN/creatinine ratio of < 20:1
Adult Diagnosis
Required Documentation
Required Tests
Adult GHD of Childhood-onset
(idiopathic)

 Recent serum IGF-I <84ng/ml
Baseline serum IGF-1

Adult GHD of Childhood-onset
with known cause
Adult-onset GHD
Documentation to support the diagnosis of
idiopathic childhood-onset GHD
Documentation that growth hormone was not
taken for 1-3 months before repeat GH
stimulation test and IGF-1 were drawn
Documentation to support the diagnosis of
childhood-onset GHD due to a known cause:
 Irreversible hypothalamic-pituitary structural
lesions: e.g., anencephaly, pituitary aplasia
 Genetic disorders: PROP1 and PIT1 mutations,
septo-optic dysplasia
 Acquired causes: pituitary tumors*,
craniopharyngeomas, cranial irradiation, brain
surgery, head trauma, CNS infections
Note: For conditions other than GHD, such as
Turner Syndrome, there is no proven benefit to
continuing GH treatment into adulthood once
final height is achieved.
Documentation to support the diagnosis of GHD
acquired as an adult due to a known cause:
Surgery, cranial irradiation, Panhypopituitarism (at
least 3 pituitary hormone deficiencies)
Traumatic brain injury and aneurysmal
subarachnoid hemorrhage: GHD may be transient;
therefore, GH stimulation testing should be
performed at least 12 months after the event

Growth hormone stimulation test:
 Insulin Tolerance Test (ITT) is
considered the Gold Standard – peak
≤ 5ng/ml (by RIA) or <2.5 ng/ml by
IRMA)
 Arginine peak ≤ 0.4ng/ml.
Note: Levodopa and clonidine tests are not
recommended
Baseline serum IGF-1
 Recent serum IGF-I <84ng/ml
Baseline serum IGF-1
 Recent serum IGF-I <84ng/ml
Baseline serum IGF-1
 Growth hormone stimulation test:
 Insulin Tolerance Test (ITT) is
considered the Gold Standard – peak
≤ 5ng/ml (by RIA) or <2.5 ng/ml by
IRMA)
 Arginine peak ≤ 0.4ng/ml.
5
Last Review: 01/2013
PARP Approval 05/2013
AETNA BETTER HEALTH OF PENNSYLVANIA
Clinical Practice Guideline
Note: Levodopa and clonidine tests are not
recommended
Adult HIV or AIDS
Wasting/cachexia
(Serostim):





Short Bowel Syndrome
(SBS) (Zorbtive):

For treatment of excess
abdominal fat in HIVinfected patients with
lipodystrophy (Egrifta):









For treatment of
Acromegaly (Somavert):





Height, weight, IBW, usual weight
Progressive weight loss below IBW (or usual body weight if usual weight <IBW) over
the last year
Dietary consult and dietary modifications over the past 3 months with documented
adequate caloric intake
Metabolic panel to r/o volume depletion- look for a BUN/creatinine ratio of < 20:1
Contraindication, Intolerance or Failure of megestrol and Marinol (dronabinol),
testosterone
Age >18 years of age
Documentation Patient is receiving specialized nutrition (i.e., TPN, PPN)
No tesamorelin and/or mannitol hypersensitivity
18-65 years of age
No evidence of active neoplastic disease per medical records
No evidence of acute critical illness per medical records
No disruption of the hypothalamic-pituitary axis (e.g. hypothalamic-pituitary-adrenal
(HPA) suppression) due to hypophysectomy, hypopituitarism, pituitary tumor/surgery,
radiation therapy of the head or head trauma
Documentation to support member is not using Egrifta for weight loss
Documentation to support member is at risk for medical complications due to excess
abdominal fat
If female, patient is not pregnant and is using a reliable form of birth control
(pregnancy category X)
Patient is 18 years of age or older
No hypersensitivity to pegvisomant or any of its ingredients
Medical records support the diagnosis of acromegaly
Medical records support failure of octreotide, Sandostatin LAR Depot or
lanreotide/Somatuline Depot
Baseline serium growth hormone, IGF-1 level and LFTs
6
Last Review: 01/2013
PARP Approval 05/2013
AETNA BETTER HEALTH OF PENNSYLVANIA
Clinical Practice Guideline
References:
1.
2.
3.
4.
5.
6.
National Institute for Health and Clinical Excellence (NICE). Human growth hormone (somatropin) for the treatment of
growth failure in children. London (UK): National Institute for Health and Clinical Excellence (NICE); 2010 May. 49
p. (Technology appraisal guidance; no. 188).
Clinical Pharmacology online: http://www.clinicalpharmacology-ip.com
Facts and Comparisons online: http://online.factsandcomparisons.com
American Association of Clinical Endocrinologists. American Association of Clinical Endocrinologists medical guidelines
for clinical practice for growth hormone use in adults and children--2003 update. Endocr Pract. 2003;9:65-76.
American Association of Clinical Endocrinologists. American Association of Clinical Endocrinologists medical guidelines
for clinical practice for growth hormone use in growth-hormone-deficient adults and transition Patients – 2009 Update.
Endocr Pract 2009;15 (Suppl 2):1-27. Accessed at
http://alt.aace.com/pub/pdf/guidelines/GrowthHormoneGuidelines.pdf on 4/18/11
Hintz RL. 2000 Consensus guidelines for the diagnosis and treatment of growth hormone deficiency in childhood and
adolescence: summary statement of the Growth Hormone Research Society on child and adolescent growth hormone
deficiency. J Clin Endocrinol Metab 2000;85:3990-3993.
7
Last Review: 01/2013
PARP Approval 05/2013