| Coverage Policy Manual | |
| Policy #: | 2024061 |
| Category: | Pharmacy |
| Initiated: | January 2025 |
| Last Review: | September 2025 |
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| Triptorelin (e.g., Triptodur, Trelstar) | |
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| Description: |
Triptorelin is a synthetic decapeptide agonist analog of gonadotropin-releasing hormone (GnRH) also known as luteinizing hormone releasing hormone (LHRH). Triptorelin is more potent than native GnRH. Triptorelin has been widely used in Europe as part of in vitro fertilization protocols and for treatment of hirsutism, endometriosis, or precocious puberty. Triptorelin is FDA-approved in the United States for the treatment of advanced prostate cancer and the treatment of central precocious puberty (CPP). Psychiatric events have been reported in patients taking GnRH agonists; patients should be observed for a potential psychiatric event or worsening of psychiatric symptoms during triptorelin treatment. Depression, including rare reports of suicidal ideation and attempt, has been reported with the use of GnRH agonists in children for CPP. In oncology, Triptorelin produces a medical castration by inhibiting the production of testosterone or estrogen through a negative feedback mechanism. After initial administration there is a transient surge in circulating levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, and estradiol.
Regulatory Status
Triptorelin
(e.g., Triptodur) was approved by the U.S. Food and Drug Administration (FDA) on June 30, 2017, for the
treatment of pediatric individuals 2 years and older with central precocious puberty (CPP).
Triptorelin
(e.g., Trelstar) was approved by the U.S. Food and Drug Administration (FDA) in 2000, for the treatment of advanced prostate cancer.
Coding
See CPT/HCPCS Code section below.
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Policy/ Coverage: |
INITIAL AND CONTINUATION APPROVAL will be for duration of treatment course or 12 months (whichever comes first). Approval timeframes may differ for members/participants of Self-Insured plans.
Effective September 2025
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
Triptorelin
(e.g., Triptodur, Trelstar)
meets member benefit certificate Primary Coverage Criteria that there be scientific evidence of effectiveness in improving health outcomes when
ALL the following criteria are met:
FDA Labeled Indications:
For FDA labeled indications, all products must be dosed in accordance with the FDA label unless otherwise specified.
ADVANCED PROSTATE CANCER
INITIAL APPROVAL:
CONTINUATION OF THERAPY:
CENTRAL PRECOCIOUS PUBERTY
INITIAL APPROVAL:
CONTINUATION OF THERAPY:
Off-label Indications:
The use of this drug for off-label indications not listed below is subject to policy 2000030.
HORMONE-SENSITIVE ADVANCED BREAST CANCER
INITIAL APPROVAL:
CONTINUATION OF THERAPY:
Please see the NCCN Drugs and Biologics Compendium for a complete list of NCCN 1 & 2A indications. To view the most recent and complete version of the guideline or Compendium, go online to NCCN.org. Please note, NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
Does Not Meet Primary Coverage Criteria Or Is Not Covered For Contracts Without Primary Coverage Criteria
Triptorelin (e.g., Trelstar, Triptodur), for any indication or circumstance not described above, does not meet member benefit certificate Primary Coverage Criteria that there be scientific evidence of effectiveness in improving health outcomes.
For members with contracts without Primary Coverage Criteria, triptorelin (e.g., Trelstar, Triptodur), for any indication or circumstance not described above, is considered
investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
POLICY GUIDELINES
ECOG Performance Status
This scale may also be referred to as the WHO (World Health Organization) or Zubrod score which is based on the following scale:
DOSAGE AND ADMINISTRATION
For FDA labeled indications, Triptorelin (e.g., Trelstar, Triptodur) must be dosed in accordance with the indication specific recommended dose per FDA label unless otherwise specified below.
For off-label indications, authorizations will not exceed the maximum FDA labeled dose and frequency across all the FDA labeled indications unless higher dose is allowed for the specific indication below.
The recommended dose of triptorelin
(e.g., Trelstar) is 3.75 mg every 4 weeks, 11.25 mg every 12 weeks or 22.5 mg every 24 weeks.
Triptorelin (e.g., Trelstar, Triptodur) is available as a 3.75 mg vial of powder for injection, 11.25 mg vial of powder for injection and 22.5 mg vial of powder for injection.
Triptorelin (e.g., Trelstar, Triptodur) should be administered as an intramuscular injection
by a healthcare professional.
Please refer to separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.
Effective January 1, 2025 to August 2025
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
Triptorelin
(e.g., Triptodur, Trelstar)
meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes when
ALL the following criteria are met:
FDA Labeled Indications:
For FDA labeled indications, all products must be dosed in accordance with the FDA label unless otherwise specified.
ADVANCED PROSTATE CANCER
INITIAL APPROVAL STANDARD REVIEW for up to 12 months:
CONTINUED APPROVAL for up to 12 months:
CENTRAL PRECOCIOUS PUBERTY
INITIAL APPROVAL STANDARD REVIEW for up to 12 months:
CONTINUED APPROVAL for up to 12 months:
Off-label Indications:
For off-label indications, authorizations will not exceed
3.75 mg once monthly OR maximum recommended doses as outlined in dosage and administration section
unless medical literature supports a higher dose.
HORMONE-SENSITIVE ADVANCED BREAST CANCER
INITIAL APPROVAL STANDARD REVIEW for up to 12
months:
CONTINUED APPROVAL for up to 12 months:
Off-label
The use of this drug is covered if an FDA-approved oncologic indication exists (not listed as an indication above) with the member meeting all the additional requirements of the prescribing information (package insert listed in the “Indications and Usage”) AND/OR a NCCN category 1 or 2A recommendation is recognized in the NCCN Drugs and Biologics Compendium with the member meeting specified criteria (See policy #2000030).
Policy Guidelines
ECOG Performance Status
This scale may also be referred to as the WHO (World Health Organization) or Zubrod score which is based on the following scale:
Dosage and Administration
Dosing per FDA Guidelines where applicable. For off-label indications, authorizations will not exceed
3.75 mg once monthly OR maximum recommended doses as outlined below unless medical literature supports a higher dose.
The recommended dose of triptorelin
(e.g., Trelstar) is 3.75 mg every 4 weeks, 11.25 mg every 12 weeks or 22.5 mg every 24 weeks.
Triptorelin (e.g., Trelstar, Triptodur) is available as a 3.75 mg vial of powder for injection, 11.25 mg vial of powder for injection and 22.5 mg vial of powder for injection.
Triptorelin (e.g., Trelstar, Triptodur) should be administered as an intramuscular injection
by a healthcare professional.
Please refer to separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
Triptorelin (e.g., Trelstar, Triptodur), for any indication or circumstance not described above, does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
For members with contracts without primary coverage criteria, triptorelin (e.g., Trelstar, Triptodur), for any indication or circumstance not described above, is considered
investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
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| Rationale: |
In a single-arm open-label study, 44 children 2 to 9 years of age with CPP, 39 females and 5 males, all naïve to previous GnRH agonist treatment, were administered triptorelin 22.5 mg at a dosing interval of 24 weeks. Subjects were evaluated over two dosing intervals for 12 months. Triptorelin 22.5 mg suppressed pituitary release of LH and FSH and, consequently, gonadal secretion of estradiol in girls and testosterone in boys. At all timepoints evaluated,
≥93% of children achieved LH suppression to prepubertal levels (i.e., serum LH
≤5 IU/L 30 minutes after GnRH agonist stimulation),
≥79% of girls achieved prepubertal levels of estradiol (i.e., <20 pg/mL), and
≥80% of boys achieved prepubertal levels of testosterone (i.e., <30 ng/dL). Triptorelin arrested or reversed progression of clinical signs of puberty with 95% of children showing no increase in the bone age/chronological age ratio, and 89% showing stabilization of sexual maturation at Month 12.
Following the second triptorelin injection, 22 children (all girls) were assessed for evidence of an acute-on-chronic phenomenon (i.e., increase in basal LH >5 IU/L or serum estradiol level >20 pg/mL 48 hours after the second triptorelin injection). Of these, one girl who achieved prepubertal hormone levels prior to the second injection showed biochemical evidence of acute-on-chronic phenomenon.
Triptorelin 3.75 mg was studied in a randomized, active control trial of 277 men with advanced prostate cancer. There was no difference observed with triptorelin response between racial groups. Men were between 47 and 89 years of age (mean = 71 years). Patients received either triptorelin 3.75 mg (N = 140) or an approved GnRH agonist monthly for 9 months. The primary efficacy endpoints were both achievement of castration by Day 29 and maintenance of castration from Day 57 through Day 253. Castration levels of serum testosterone (≤ 1.735 nmol/L; equivalent to 50 ng/dL) in patients treated with triptorelin 3.75 mg were achieved at Day 29 in 125 of 137 (91.2%) patients and at Day 57 in 97.7% of patients. Maintenance of castration levels of serum testosterone from Day 57 through Day 253 was found in 96.2% of patients treated with triptorelin 3.75 mg. The presence of an acute-on-chronic flare phenomenon was also studied as a secondary efficacy endpoint. Serum LH levels were measured at 2 hours after repeating triptorelin 3.75 mg administration on Days 85 and 169. One hundred twenty-four of the 126 evaluable patients (98.4%) on Day 85 had a serum LH level of ≤ 1.0 IU/L at 2 hours after dosing, indicating desensitization of the pituitary gonadotroph receptors.
Triptorelin 11.25 mg was studied in a randomized, active control trial of 346 men with advanced prostate cancer. There was no difference observed with triptorelin response between racial groups. Men were between 45 and 96 years of age (mean = 71 years). Patients received either triptorelin 11.25 mg (N = 174) every 12 weeks for a total of up to 3 doses (maximum treatment period of 253 days) or triptorelin 3.75 mg (N = 172) every 28 days for a total of up to 9 doses. The primary efficacy endpoints were both achievement of castration by Day 29 and maintenance of castration from Day 57 through Day 253. Castration levels of serum testosterone (≤ 1.735 nmol/L; equivalent to 50 ng/dL) were achieved at Day 29 in 167 of 171 (97.7%) patients treated with triptorelin 11.25 mg, and maintenance of castration levels of serum testosterone from Day 57 through Day 253 was found in 94.4% of patients treated with triptorelin 11.25 mg.
Triptorelin 22.5 mg was studied in a non-comparative trial of 120 men with advanced prostate cancer. The clinical trial population consisted of 64% Caucasian, 23% Black, and 13% Other, with a mean age of 71.1 years (range 51-93). Patients received triptorelin 22.5 mg (N = 120) every 24 weeks for a total of 2 doses (maximum treatment period of 337 days). The primary efficacy endpoints included achievement of castration by Day 29 and maintenance of castration from Day 57 through Day 337. Castration levels of serum testosterone (≤ 1.735 nmol/L; equivalent to 50 ng/dL) were achieved at Day 29 in 97.5% (117 of 120) of patients treated with TRELSTAR 22.5 mg. Castration was maintained in 93.3% of patients in the period from Day 57 to Day 337.
2025 Update
Annual policy review completed with a literature search using the MEDLINE database through September 2025. No new literature was identified that would prompt a change in the coverage statement.
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| CPT/HCPCS: | |
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| Group specific policy will supersede this policy when applicable. This policy does not apply to the Wal-Mart Associates Group Health Plan participants. | |
| CPT Codes Copyright © 2025 American Medical Association. | |