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Neurokinin Receptor Antagonists Prior Authorization with Quantity Limit Program Summary
Policy Number: PH-1213
This program applies to Blue Partner, Commercial, GenPlus, NetResults A series, SourceRx and Health Insurance Marketplace formularies.
POLICY REVIEW CYCLE
Effective Date |
Date of Origin |
1/1/2024 |
1/1/2024 |
FDA APPROVED INDICATIONS AND DOSAGE
Agent(s) |
FDA Indication(s) |
Notes |
Ref# |
VEOZAH™ (fezolinetant) Tablet |
Treatment of moderate to severe vasomotor symptoms due to menopause |
|
1 |
See package insert for FDA prescribing information: https://dailymed.nlm.nih.gov/dailymed/index.cfm
CLINICAL RATIONALE
Vasomotor Symptoms |
Menopause is the final stage of the ovarian physiology in patients and represents a time when reproductive function is lost due to complete depletion of finite ovarian follicle supply.(2) It is defined as 12 months of amenorrhea and occurs at a median age of 51.3 years in the United States.(1,3) While the fundamental process of menopause is related directly to ovarian aging, all aspects of the hypothalamic-pituitary-ovarian-uterine axis are altered with time.(2) Estrogen withdrawal during the menopause transition (MT) is associated with alterations in the hypothalamic thermoregulatory neutral zone, a group of neurons that regulate body temperature. Normally inhibited by estrogen, this group of hypothalamic neurons, known collectively as KNDy neurons for the co-expression of kisspeptin, neurokinin B (NKB), and dynorphin, are overstimulated during the MT and can lead to dysregulation of body temperature. These changes lead to an increased frequency of bodily reaction to both internal and environmental triggers that prevent heat loss. Vasomotor symptoms (VMS), also known as hot flashes, are known as the hallmark manifestations of the MT which include feelings of flushing, warmth sensation, skin reddening, and perspiration.(2,3) Symptoms of menopause are most prevalent and severe during the first 1 to 2 years after the final menstrual period (FMP). Some patients will experience bothersome symptoms for more than a decade. VMS affect as many as 80% of midlife patients. Moderate to severe VMS (i.e., 7 or more episodes per day or 50-60 episodes per week) affects 32% to 46% percent of patients undergoing menopause. Data show that patients who experience frequent VMS (greater than 6 days in the previous 2 weeks) also experience higher rates of anxiety, depression, difficulty sleeping and overall impaired quality of life.(1,2,3,5) Frequent VMS persisted on average 7.4 years in the Study of Women's Health Across the Nation and appear to be linked to cardiovascular, bone, and cognitive risks.(6) Hormone therapy (HT) remains the gold standard, most effective treatment for relief of VMS and has been shown to prevent bone loss and fracture.(3,6) Patients with significant sleep or mood disturbance during the MT may also benefit from HT. HT reduces symptom frequency by 75% and symptom severity by 90%, usually within one month of initiation.(3,6) In the Women's Health Initiative (WHI), patients with VMS experienced an 85% reduction in symptoms after treatment with estrogen plus progesterone.(2) For patients 60 years of age or younger who are within 10 years of menopause onset and have no contraindications, the benefit-risk ratio is favorable for hormone treatment of bothersome VMS. HT are considered safe and effective in low-risk patients without underlying coronary heart disease or history of breast cancer. Generally well tolerated, the most common acute adverse effects of HT are breast pain and uterine bleeding. HT has been shown to improve glycemic control and insulin resistance in patients with and without type 2 diabetes, as well as other cardiovascular disease risk factors such as lipid profile. For patients more than 10 years /from menopause onset or 60 years or older who initiate hormone therapy, the benefit-risk ration appears less favorable because of greater absolute risks of CHD, stroke, VTE, and dementia.(2,3,6) Estrogen regimens are available as estrogen-only, combined with progestin, or combined with a serum estrogen receptor modulator (SERM).(2) Systemic estrogens can be prescribed as oral drugs; transdermal patches, sprays and gels; or as vaginal rings. Meta-analysis of estrogen preparations found no evidence of a significant difference between transdermal and oral preparations for alleviating VMS. Estrogen-alone therapy (ET) can be used for symptomatic patients without a uterus and estrogen plus progesterone therapy (EPT) or tissue-selective estrogen complex (TSEC) for patients with a uterus to protect against endometrial neoplasia.(6) Vaginal formulations do not require progestin as these have not been shown to induce endometrial proliferation.(2) Nonhormone options are important considerations for patients who are not good candidates for HT.(7) Paroxetine 7.5 mg was the first nonhormonal pharmaceutical FDA approved for the treatment of moderate to severe VMS, with improvements found in VMS severity and frequency for up to 24 months, along with improvements in sleep disruption, without weight gain or negative effects on libido. Other nonhormone medications that are recommended to reduce VMS include selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), gabapentin, oxybutynin. Paroxetine, escitalopram, citalopram, venlafaxine, and desvenlafaxine have been shown to significantly reduce VMS in large, double-blind, randomized, controlled trials (RCTs) of symptomatic patients. Trends towards improvement have been seen with sertraline and fluoxetine but were statistically insignificant, therefore, not recommended. Duloxetine has been found to reduce VMS in smaller studies. Hot flash reductions vary from 25% to 69% with these treatments, with improvement in composite hot flash severity and frequency from 27 to 61%. A pooled analysis from three RCTs showed that 10 mg to 20 mg of escitalopram, 0.5 mg of oral 17-beta-estradiol, and 75 mg of venlafaxine daily resulted in comparable reductions of VMS frequency. Gabapentin, an antiepileptic drug, has shown that it has improved the frequency and severity of VMS in several trial studying the dose of 900 mg/day. Gabapentin at higher doses (titrated to 2,400 mg/d) has been shown to be as beneficial as estrogen (conjugated equine estrogens 0.625 mg/d) in reducing hot flash scores. Oxybutynin, an antimuscarinic, anticholinergic therapy, demonstrated in one prospective study and two randomized double-blind studies in postmenopausal patients, that doses ranging from 2.5 mg or 5 mg twice daily up to 15 mg extended-release daily, significantly improved moderate to severe VMS.(7) |
Safety(1) |
VEOZAH is a neurokinin 3 (NK3) receptor antagonist that blocked the neurokinin B (NKB) binding on the kisspeptin/neurokinin B/dynorphin (KNDy) neuron to modulate neuronal activity in the thermoregulatory center. Elevations in serum transaminase levels greater than three times the upper limit of normal (ULN) occurred in 2.3% of women receiving VEOZAH. Labeling recommends baseline bloodwork be evaluated for hepatic function and injury prior to VEOZAH initiation. If baseline hepatic transaminase evaluation is less than two times the ULN and the total bilirubin is normal, VEOZAH can be initiated. Follow up evaluations of hepatic transaminase concentrations are recommended at 3, 6, and 9 months after initiation or when symptoms suggest liver injury.(1) VEOZAH is contraindicated in women with any of the following indications:
|
REFERENCES
Number |
Reference |
1 |
VEOZAH prescribing information. Astellas Pharma US LLC. May 2023. |
2 |
Santoro N, et al. The Menopause Transition: Signs, Symptoms, and Management Options. The Journal of Clinical Endocrinology & Metabolism, Jan 2021; 106(1): 1-15. https://doi.org/10.1210/clinem/dgaa764 |
3 |
Khan SJ, Kapoor E, Faubion SS, Kling JM. Vasomotor Symptoms During Menopause: A Practical Guide on Current Treatments and Future Perspectives. Int J Womens Health. 2023 Feb 14;15:273-287. doi:10.2147/IJWH.S365808. |
4 |
Avis NE, Crawford SL, Greendale G, et al. Duration of Menopausal Vasomotor Symptoms Over the Menopause Transition. JAMA Intern Med. 2015;175(4):531–539. doi:10.1001/jamainternmed.2014.8063. |
5 |
Beaudoin FL, et al. Fezolinetant for Moderate to Severe Vasomotor Symptoms Associated with Menopause: Effectiveness and Value; Final Evidence Report. Institute for Clinical and Economic Review, January 23, 2023. https://icer.org/assessment/vasomotor-symptoms-menopause-2022/#overview |
6 |
The 2022 hormone therapy position statement of The North American Menopause Society. (2022). Menopause, 29(7), 767–794. DOI: 10.1097/GME.0000000000002028. |
7 |
The 2023 nonhormone therapy position statement of The North American Menopause Society. (2023). Menopause, 30(6), 573-590. DOI: 10.1097/GME.0000000000002200. |
POLICY AGENT SUMMARY PRIOR AUTHORIZATION
Target Brand Agent(s) |
Target Generic Agent(s) |
Strength |
Targeted MSC |
Available MSC |
Final Age Limit |
Preferred Status |
|
||||||
Veozah |
fezolinetant tab |
45 MG |
M ; N ; O ; Y |
N |
|
|
POLICY AGENT SUMMARY QUANTITY LIMIT
Target Brand Agent Name(s) |
Target Generic Agent Name(s) |
Strength |
QL Amount |
Dose Form |
Day Supply |
Duration |
Addtl QL Info |
Allowed Exceptions |
Targeted NDCs When Exclusions Exist |
|
|||||||||
Veozah |
fezolinetant tab |
45 MG |
30 |
Tablet |
30 |
DAYS |
|
|
|
CLIENT SUMMARY – PRIOR AUTHORIZATION
Target Brand Agent Name(s) |
Target Generic Agent Name(s) |
Strength |
Client Formulary |
Veozah |
fezolinetant tab |
45 MG |
Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx |
CLIENT SUMMARY – QUANTITY LIMITS
Target Brand Agent Name(s) |
Target Generic Agent Name(s) |
Strength |
Client Formulary |
Veozah |
fezolinetant tab |
45 MG |
Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx |
PRIOR AUTHORIZATION CLINICAL CRITERIA FOR APPROVAL
Module |
Clinical Criteria for Approval |
||
|
Initial Evaluation Target Agent(s) will be approved when BOTH of the following are met:
Length of Approval: 3 months NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria.
Renewal Evaluation Target Agent(s) will be approved when ALL of the following are met:
Length of Approval: 12 months NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria. |
QUANTITY LIMIT CLINICAL CRITERIA FOR APPROVAL
Module |
Clinical Criteria for Approval |
|
Quantity limit for the Target Agent(s) will be approved when ONE of the following is met:
Length of approval: 3 months for Initial; 12 months for Renewal |
This pharmacy policy is not an authorization, certification, explanation of benefits or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All pharmacy policies are based on (i) information in FDA approved package inserts (and black box warning, alerts, or other information disseminated by the FDA as applicable); (ii) research of current medical and pharmacy literature; and/or (iii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.
The purpose of Blue Cross and Blue Shield of Alabama’s pharmacy policies are to provide a guide to coverage. Pharmacy policies are not intended to dictate to physicians how to practice medicine. Physicians should exercise their medical judgment in providing the care they feel is most appropriate for their patients.
Neither this policy, nor the successful adjudication of a pharmacy claim, is guarantee of payment.
Commercial _ PS _ Neurokinin Receptor Antagonists _PAQL _ProgSum_ 1/1/2024