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
  • Growth Hormone Deficiency (Pediatric and Adult populations)
  • Growth failure associated with Prader-Willi Syndrome
  • Short stature born SGA with no catch-up growth by 2 to 4 years of age (>2 yrs old)
  • Growth failure associated with associated with Turner Syndrome
  • Idiopathic Short Stature (Pediatric population -NOT MEDICALLY NECESSARY FOR THIS INDICATION)
  • Humatrope
  • Growth Hormone Deficiency (Pediatric and Adult populations)
  • Short stature born SGA with no catch-up growth by 2 to 4 years of age (>2 yrs old)
  • Growth failure associated with associated with Turner Syndrome
  • Idiopathic Short Stature (Pediatric population -NOT MEDICALLY NECESSARY FOR THIS INDICATION)
  • Short stature homeobox–containing gene deficiency (SHOX deficiency - Pediatric population)
  • Norditropin
  • Growth Hormone Deficiency (Pediatric and Adult populations)
  • Short stature born SGA with no catch-up growth by 2 to 4 years of age (>2 yrs old)
  • Growth failure associated with associated with Turner Syndrome
  • Growth failure associated with Noonan syndrome
  • Nutropin, (Nutropin AQ, Nutropin AQ NuSpin)
  • Growth Hormone Deficiency (Pediatric and Adult populations)
  • Short stature born SGA with no catch-up growth by 2 to 4 years of age (>2 yrs old)
  • Idiopathic Short Stature (Pediatric population -NOT MEDICALLY NECESSARY FOR THIS INDICATION)
  • Growth failure associated with chronic renal insufficiency
  • Omnitrope, Saizen
  • Growth Hormone Deficiency (Pediatric and Adult populations)
  • Tev-Tropin
  • Growth Hormone Deficiency (Pediatric populations)
  • Growth failure associated with Prader-Willi Syndrome
  • Valtropin
  • Growth Hormone Deficiency (Pediatric and Adult populations)
  • Growth failure associated with associated with Turner Syndrome
  • Iplex, Increlex (Limited Access)
  • IGF-1 deficiency
  • Serostim
  • HIV-associated failure to thrive in children (off-label use)
  • AIDS-associated wasting syndrome, or cachexia in adults
  • Zorbtive
  • Short-bowel syndrome in adult patients receiving specialized nutritional support
  • Egrifta
  • For treatment of excess abdominal fat in HIV-infected patients with lipodystrophy
  • Somavert
  • 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

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

Pediatrics Diagnosis / Required documentation
GHD
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. /
  • Recent (within the last 3 months) height and weightand pretreatmentgrowth 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), orPeak <5 ng/ml (by IRMA)
1 agent with peak level required if cause is known:
  • Structural or developmental abnormalities: anencephaly, pituitary aplasia
  • Genetic disorders: e.g., PROP1 and PIT1 mutations, septo-optic dysplasia
  • Acquired causes: e.g., craniopharyngeomas*, cranial irradiation, brain surgery, head trauma, CNS infections
2 agents with peak levels required if cause is unknown (idiopathic).
Turner Syndrome (TS), Prader-Willi Syndrome,
SHOX deficiency, or Noonan Syndrome /
  • 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)

Chronic Renal Insufficiency (CRI) /
  • 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)

Small for Gestational Age (SGA) with failure to catch-up by
2-4 years of age /
  • 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
  • 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)

IGF-1 Deficiency
(Increlex only) /
  • ≥ 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
  • basal IGF-1 standard deviation score less than or equal to −3
  • normal or elevated growth hormone levels

Pediatric patients: HIV-associated failure to thrive (Serostim): (off label) /
  • 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) /
  • 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
/
  • 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)
Argininepeak ≤ 0.4ng/ml.
Note: Levodopa and clonidine tests are not recommended
Adult GHD of Childhood-onset with known cause / 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. / Baseline serum IGF-1
Adult-onset GHD / 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) /
  • Recent serum IGF-I <84ng/ml
Baseline serum IGF-1
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 /
  • 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)
Argininepeak ≤ 0.4ng/ml.
Note: Levodopa and clonidine tests are not recommended
Adult HIV or AIDS Wasting/cachexia (Serostim): /
  • 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

Short Bowel Syndrome (SBS) (Zorbtive): /
  • Age >18 years of age
  • Documentation Patient is receiving specialized nutrition (i.e., TPN, PPN)

For treatment of excess abdominal fat in HIV-infected patients with lipodystrophy (Egrifta): /
  • 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)

For treatment of Acromegaly (Somavert): /
  • 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

References:

  1. 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).
  2. Clinical Pharmacology online:
  3. Facts and Comparisons online:
  4. 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.EndocrPract. 2003;9:65-76.
  5. 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. EndocrPract 2009;15 (Suppl 2):1-27. Accessed at on 4/18/11
  6. 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 ClinEndocrinolMetab 2000;85:3990-3993.

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Last Review: 01/2013

PARP Approval 05/2013