Leuprolide acetate (Lupron®, Lupron Depot ®, Lupron Depot-Ped ®, Eligard®, Fensolvi™) and leuprolide mesylate (Camcevi^TM) are synthetic analogs of gonadotropin releasing hormone (GnRH). Although leuprolide has potent GnRH agonist properties during short-term or intermittent therapy, the principal effect of the drug during long-term administration is inhibition of gonadotropin secretion and suppression of ovarian and testicular steroidogenesis.

Leuprolide and norethindrone (Lupaneta®) is a combination medicine used to treat symptoms of endometriosis.

Triptorelin extended-release (Triptodur®) and triptorelin pamoate (Trelstar®) are synthetic decapeptide agonist analogs of GnRH that reversibly inhibits gonadotropin secretion when administered in continuous doses.

Histrelin (Vantas®, Supprelin LA®) is a synthetic nonapeptide analog of GnRH. Contained in an implant, histrelin (Vantas, Supprelin LA) is released via a diffusion-controlled hydrogel polymer reservoir. Histrelin (Vantas, Supprelin LA) functions as a GnRH agonist, and is a potent inhibitor of gonadotropin secretion when administered in continuous doses.

Delaware Mandate:

Effective September 1, 2017, 18 Delaware Code §§3338B and 3555B, require that no individual or group or blanket policy or contract of health insurance, or certificate issued thereunder, which is delivered, issued for delivery, renewed, modified, altered, or amended in this State by any health insurer, health service corporation or health maintenance organization that directly or indirectly covers the treatment of cancer shall limit or exclude coverage for a drug approved by the United States Food and Drug Administration by mandating that the insured shall first be required to fail to successfully respond to a different drug or drugs or prove a history of failure of such drug or drugs; provided, however that the use of such drug or drugs is consistent with best practices for the treatment of stage 4 advanced, metastatic cancer or, in the case of other cancers, the use of the drug is supported by national clinical guidelines, national standards of care, or peer reviewed medical literature for the treatment of the cancer, or in the case of targeted therapy, the target at issue.

The use of leuprolide acetate (Lupron) may be considered medically necessary for the following conditions: 

Anemia due to Uterine Fibroids

• For the preoperative treatment of anemia due to uterine fibroids in combination with iron supplementation when iron therapy alone fails to correct the anemia:
  • Duration of therapy not to exceed three (3) months; or

Central Precocious Puberty

• For treatment of children with central precocious puberty when ALL the following criteria are met:
  • Confirmed clinical diagnosis of CPP defined by the following:
    • Measurement of LH and FSH following stimulation with a GnRH analog; and
    • Bone age versus chronological age assessment supports diagnosis of CPP; and
  • Individual has onset of secondary sexual characteristics;
    • Less than 11 years of age for females; or
    • Less than 12 years of age for males; and
  • Initial authorization will be for a period of 12 months.

Reauthorization criteria

• Reauthorization of leuprolide acetate (Lupron) may be considered medically necessary when ALL of the following criteria are met:
  • Individual is currently receiving therapy; and
  • Documentation of positive clinical response (e.g. pre-pubertal slowing or decline, normalization of FSH or LH, or normalization of bone age); and
  • Reauthorization will be for a period of 12 months.

Endometriosis

• For the management of endometriosis, including pain relief and reduction of endometriotic lesions; or
• Duration of initial treatment or retreatment not to exceed six (6) months; or

Prostate Cancer

• As palliative treatment of advanced prostate cancer; or

Compendia Sources

• Leuprolide acetate (Lupron) may be considered medically necessary for treatment of any of the current category 1, 2A, or 2B NCCN recommendations.

The use of leuprolide/leuprolide acetate (Lupron) not meeting the criteria as indicated in this policy is considered experimental/investigational and therefore non-covered because the safety and/or effectiveness of this service cannot be established by the available published peer-reviewed literature.

The use of leuprolide acetate for depot suspension (Lupron Depot) may be considered medically necessary for ANY of the following conditions:

Anemia due to Uterine Fibroids

• The preoperative treatment of anemia due to uterine fibroids in combination with iron supplementation when iron therapy alone fails to correct the anemia:
  • Duration of therapy not to exceed three (3) months and limited to one injection; or

Endometriosis

• The management of endometriosis, including pain relief and reduction of endometriotic lesions:
  • Duration of initial treatment or retreatment not to exceed six (6) months; or
• As initial management of painful symptoms of endometriosis and for management of recurrence of symptoms in combination with norethindrone acetate 5 mg tablet taken once daily as add-back therapy:
  • Duration of initial treatment or retreatment not to exceed six (6) months; or

Prostate Cancer

• The palliative treatment of advanced prostatic cancer; or

Compendia Sources

• Leuprolide acetate for depot suspension (Lupron Depot) may be considered medically necessary for treatment of any of the current category 1, 2A, or 2B NCCN recommendations.

The use of leuprolide acetate for depot suspension (Lupron Depot) not meeting the criteria as indicated in this policy is considered experimental/investigational and therefore non-covered because the safety and/or effectiveness of this service cannot be established by the available published peer-reviewed literature.

       The use of leuprolide acetate for depot suspension (Lupron Depot Ped) may be considered medically necessary for the treatment of children with central precocious puberty: when ALL the following criteria are met:

Leuprolide and norethindrone (Lupaneta Pack) may be considered medically necessary for women 18 years of age and older for:

• The initial management of the painful symptoms of endometriosis; or
• The management of recurrence of symptoms.

Initial treatment course is limited to six (6) months and use is not recommended longer than a total of 12 months due to concerns about adverse impact on bone mineral density.

The use of leuprolide and norethindrone (Lupaneta Pack) not meeting the criteria as indicated in this policy is considered experimental/investigational and therefore non-covered because the safety and/or effectiveness of this service cannot be established by the available published peer-reviewed literature.

The use of leuprolide acetate (Eligard) may be considered medically necessary for the following conditions:

Prostate Cancer

• As palliative treatment of advanced prostate cancer; or     

Compendia Sources

• Leuprolide acetate (Eligard) may be considered medically necessary for treatment of any of the current category 1, 2A, or 2B NCCN recommendations.

The use of leuprolide acetate (Eligard) not meeting the criteria as indicated in this policy is considered experimental/investigational and therefore non-covered because the safety and/or effectiveness of this service cannot be established by the available published peer-reviewed literature.

Leuprolide acetate (Fensolvi) may be considered medically necessary for the following condition:

Central Precocious Puberty

• For the treatment of pediatric individuals two (2) years of age and older with central precocious puberty when ALL the following criteria are met:
  • Confirmed clinical diagnosis of CPP defined by the following:
    • Measurement of LH and FSH elevated following stimulation with a GnRH analog; and
    • Assessment confirms bone age advancement beyond chronological age; and
  • Individual has onset of secondary sexual characteristics
    • Less than 11 years of age for females; or
    • Less than 12 years of age for males; and
• Initial authorization will be for a period of 12 months.

Reauthorization criteria

• Reauthorization of leuprolide acetate (Fensolvi) may be considered medically necessary when ALL of the following criteria are met:
  • Individual is currently receiving therapy; and
    
  • Documentation of positive clinical response (e.g. pre-pubertal slowing or decline, normalization of FSH or LH, or normalization of bone age); and
  • Reauthorization will be for a period of 12 months.

The use of leuprolide acetate (Fensolvi) not meeting the criteria as indicated in this policy is considered experimental/investigational and therefore non-covered because the safety and/or effectiveness of this service cannot be established by the available published peer-reviewed literature.

Leuprolide mesylate (Camcevi) may be considered medically necessary for the following condition: 

Prostate Cancer

• For the treatment of adult individuals with advanced prostate cancer; or

Compendia Sources

• Leuprolide mesylate (Camcevi) may be considered medically necessary for treatment of any of the current category 1, 2A, or 2B NCCN recommendations.

The use of leuprolide mesylate (Camcevi) not meeting the criteria as indicated in this policy is considered experimental/investigational and therefore non-covered because the safety and/or effectiveness of this service cannot be established by the available published peer-reviewed literature.

The use of triptorelin extended-release (Triptodur) may be considered medically necessary for the treatment of pediatric individuals two (2) years or older with central precocious puberty (CPP) when ALL the following criteria are met:

Central Precocious Puberty

• Confirmed clinical diagnosis of CPP by the following:
  • Measurement of LH and FSH elevated following stimulation with a GnRH analog; and
  • Assessment confirms bone age advancement beyond chronological age; and
• Individual has onset of secondary sexual characteristics
  • Less than 11 years of age for females; or
  • Less than 12 years of age for males; and
• Initial authorization will be for a period of 12 months.

Reauthorization criteria

• Reauthorization of triptorelin extended-release (Triptodur) may be considered medically necessary when ALL of the following criteria are met:
  • Individual is currently receiving therapy; and
  • Documentation of positive clinical response (e.g. pre-pubertal slowing or decline, normalization of FSH or LH, or normalization of bone age); and
  • Reauthorization will be for a period of 12 months.

The use of triptorelin extended-release (Triptodur) not meeting the criteria as indicated in this policy is considered experimental/investigational and therefore non-covered because the safety and/or effectiveness of this service cannot be established by the available published peer-reviewed literature.

The use of triptorelin pamoate (Trelstar) may be considered medically necessary for the following conditions:

Prostate Cancer

• The palliative treatment of advanced prostate cancer; or

Compendia Sources

Triptorelin pamoate (Trelstar) may be considered medically necessary for treatment of any of the current category 1, 2A, or 2B NCCN recommendations.

The use of triptorelin pamoate (Trelstar) not meeting the criteria as indicated in this policy is considered experimental/investigational and therefore non-covered because the safety and/or effectiveness of this service cannot be established by the available published peer-reviewed literature.

The use of histrelin acetate subcutaneous implant (Vantas) may be considered medically necessary for the following conditions:

Prostate Cancer

• For the palliative treatment of advanced prostate cancer; or

Compendia Sources

• Histrelin acetate subcutaneous implant (Vantas) may be considered medically necessary for treatment of any of the current category 1, 2A, or 2B NCCN recommendations.

The use of histrelin acetate subcutaneous implant (Vantas) for any other indication is considered not medically necessary, and therefore, non-covered.

The use of histrelin acetate subcutaneous implant (Vantas) not meeting the criteria as indicated in this policy is considered experimental/investigational and therefore non-covered because the safety and/or effectiveness of this service cannot be established by the available published peer-reviewed literature.

The use of histrelin acetate subcutaneous implant (Supprelin LA) may be considered medically necessary for the following condition:

Central Precocious Puberty (CPP)

• For treatment of children with central precocious puberty when ALL the following criteria are met:

o   Confirmed clinical diagnosis of CPP defined by any of the following:

§  Measurement of LH and FSH elevated following stimulation with a GnRH analog; and

§  Assessment confirms bone age advancement beyond chronological age; and

o   Individual has onset of secondary sexual characteristics;

§  Less than 11 years of age for females; or

§  Less than 12 years of age for males; and

o   Initial authorization will be for a period of 12 months.

Reauthorization criteria

• Reauthorization of histrelin acetate subcutaneous implant (Supprelin LA) may be considered medically necessary when ALL of the following criteria are met:
  • Individual is currently receiving therapy; and
  • Documentation of positive clinical response (e.g. pre-pubertal slowing or decline, normalization of FSH or LH, or normalization of bone age); and
  • Reauthorization will be for a period of 12 months.

The use of histrelin acetate subcutaneous implant (Supprelin LA) not meeting the criteria as indicated in this policy is considered experimental/investigational and therefore non-covered because the safety and/or effectiveness of this service cannot be established by the available published peer-reviewed literature.

Other Medically Accepted Non-FDA Approved Indications, Class IIb or Higher Grade Recommendations

The use of histrelin acetate (Supprelin LA, Vantas), leuprolide acetate (Lupron Depot, Lupron Depot-Ped Fensolvi), or triptorelin (Triptodur, Trelstar) may be considered medically necessary for puberty suppression in individuals with gender dysphoria when ALL of the following criteria are met:

• The adolescent has demonstrated a long-lasting and intense pattern of gender non-conformity or gender dysphoria (whether suppressed or expressed); and
• Gender dysphoria emerged or worsened with the onset of puberty; and
• Any co-existing psychological, medical, or social problems that could interfere with treatment (e.g., that may compromise treatment adherence) have been addressed, such that the adolescent’s situation and functioning are stable enough to start treatment; and
• The adolescent has given informed consent and, particularly when the adolescent has not reached the age of medical consent, the parents or other caretakers or guardians have consented to the treatment and are involved in supporting the adolescent throughout the treatment process.

The use of histrelin acetate (Supprelin LA, Vantas), leuprolide acetate (Lupron Depot, Lupron Depot-Ped), or triptorelin (Triptodur, Trelstar) not meeting the criteria as indicated in this policy is considered experimental/investigational and therefore non-covered because the safety and/or effectiveness of this service cannot be established by the available published peer-reviewed literature.

NOTE*: First generation antiandrogen must be given for seven (7) or more days to prevent testosterone flare if metastases are present in weight-bearing bone.

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NOTE: Men with breast cancer should be treated similarly to postmenopausal women, except that use of an aromatase inhibitor is ineffective without concomitant suppression of testicular steroidogenesis.

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NOTE: In addition to the above criteria, product specific dosage and/or frequency limits may apply in accordance with the U.S. Food and Drug Administration (FDA)-approved product prescribing information, national compendia, Centers for Medicare and Medicaid Services (CMS) and other peer reviewed resources or evidence-based guidelines. Highmark may deny, in full or in part, reimbursement for utilization that does not fall within the applicable dosage and/or frequency limits.