Support for you and your patients

View and download information and resources to make choosing NEXTSTELLIS® for your patients easy

Medical Affairs

 

Request Sample

 

Letter of Medical Necessity

Is NEXTSTELLIS covered by your patient’s insurer?

If it is not on the insurer’s prescription drug formulary or if the plan requires prior authorization, complete the form and send it to your patient’s insurer to request coverage of NEXTSTELLIS.

Patient Brochure

Brochure for your patients to:

  • Explain what NEXTSTELLIS is and why it is different
  • Show what to expect from NEXTSTELLIS
  • How to start taking NEXTSTELLIS

Request a Mayne Pharma Representative

If you would like more information, or have any questions, about NEXTSTELLIS, then please submit a request: for example, on our product availability, savings program, sampling, and our pre-activated Saving Cards or for details on our patient support services.

NEXTSTELLIS® is now $0* copay for most insured, covered, eligible patients

Most uncovered, insured eligible patients will pay as little as $25 for each one-month prescription fill or as little as $50 (less than $17 per month) for each three-month prescription fill.

Easy way to access the savings program is to send your patient prescriptions to one of our hub services

Download Provider Information

GoodRX Prescription Services
BlinkRx

  • No copay card required
  • If applicable patient insurance will be applied
  • Cash option available
  • Free home delivery

For patients filling a prescription at large retail pharmacies, a copay card may be required to access savings

NEXTSTELLIS copay card

*Depending on insurance coverage, eligible patients may pay as little as $0 for each of up to 12 one-month NEXTSTELLIS prescription fills OR each of up to 4 three-month NEXTSTELLIS prescription fills. Check with pharmacist for copay discount. Maximum savings limits apply; patient out-of-pocket expense will vary. Offer not valid for patients enrolled in Medicare, Medicaid, or other federal or state healthcare programs. Please see Program Terms, Conditions, and Eligibility Criteria here.

Questions about estetrol (E4)

Estetrol is the first native estrogen approved for contraceptive use in the United States. Produced during pregnancy, estetrol is found at high levels in maternal–fetal circulation. For pharmaceutical use, estetrol can be produced from plants and offers a distinct pharmacologic profile from other contraceptive estrogens. Estetrol has selective actions on nuclear estrogen receptors and is the first estrogen to be described as a NEST: a Native Estrogen with Selective actions in Tissues.1-5 Find more information about how estetrol works.

Estetrol is a Native Estrogen with Selective actions in Tissues (NEST).3 This describes several qualities that make estetrol unique. First, estetrol is an endogenous estrogen that occurs naturally during pregnancy.1,6 Second, it binds selectively to nuclear estrogen receptors while blocking estrogen receptors in the membrane. This makes estetrol pharmacologically distinct from other estrogens that bind both membrane and nuclear estrogen receptors throughout the body.7 Learn more about estetrol (E4) and its binding activity.

Tissues in the body respond differently to estrogen based on their dependence on nuclear or membrane receptor signaling.7,8

  • Other contraceptive estrogens bind widely to 2 main types of estrogen receptor—nuclear ERα and membrane ERα7,9,10
  • Estetrol binds selectively to nuclear estrogen receptors while blocking estrogen receptors in the membrane3

Understanding the role of nuclear and membrane estrogen receptor signaling in different tissue types helps clarify the selective actions of estetrol.11-14

Learn more about estetrol (E4)

In clinical trials, NEXTSTELLIS demonstrated a highly predictable bleeding profile. Unscheduled bleeding with NEXTSTELLIS occurred in <2% of women in the trial, and the average duration of spotting or bleeding episodes was <1 day.15 Learn more about the bleeding patterns in Phase III studies of NEXTSTELLIS.

Estetrol is an endogenous estrogen that occurs naturally during pregnancy. For pharmaceutical use, estetrol is produced from a plant source.2

Questions about NEXTSTELLIS

NEXTSTELLIS pairs DRSP, a proven progestin, with the first newly approved contraceptive estrogen in 60 years—estetrol (E4).6,17,10 Estetrol binds selectively with nuclear estrogen receptor alpha (ERα) and antagonizes membrane ERα.7 Tissues in the body respond differently to estrogen based on their dependence on nuclear or membrane receptor signaling. This is what gives estetrol its unique tissue selectivity.7,8

Yes, NEXTSTELLIS is a monophasic regimen with 24 active and 4 placebo pills per 28-day cycle pack.6

Estetrol—the estrogen component in NEXTSTELLIS—was studied (Phase II studies) in combination with drospirenone and levonorgestrel.6,17 Estetrol combined with either DRSP or LNG demonstrated adequate safety and efficacy.22 However, these and other Phase II studies also evaluated18,19,20,21:

  • Bleeding patterns
  • Hemostatic parameters
  • Endocrine parameters (including SHBG),
  • Lipid and carbohydrate metabolism parameters
  • Ovulation inhibition.

Based on the results of these studies, drospirenone was selected as the optimal progestin to combine with estetrol.

There are 3 key differences between estetrol and ethinyl estradiol that make a comparison in doses difficult:

  1. Estetrol is selective for nuclear ERα, whereas other contraceptive estrogens bind widely to both nuclear and membrane ERα3,7,9,10
    • Tissues in the body respond differently to estrogen based on their dependence on nuclear or membrane receptor signaling7,8
    • Estetrol activates nuclear ERα but antagonizes membrane ERα3
    • This is what gives estetrol its tissue selectivity3
    • Depending on the tissue, the differential effects of estetrol vs ethinyl estradiol will vary3,7,9
  2. Estetrol is much less potent and has lower binding affinity than ethinyl estradiol1,4,22
    • The estrogen receptor binding affinity of estetrol is approximately 5% compared with EE4,22
    • The downstream effects of E4 receptor binding are 1%-10% that of EE1,23
  3. Estetrol is minimally metabolized by the liver, whereas ethinyl estradiol is extensively metabolized by the liver1,24

Because of these differences, the dose of E4 cannot be translated into an equivalent dose of EE that applies to all tissues.
Ultimately, it is important to remember that estetrol is fundamentally different from synthetic contraceptive estrogens such as ethinyl estradiol. The lowest effective dose of estetrol + DRSP was established in Phase II dose-finding studies and validated in the Phase III studies that were the basis of its approval.6,15

Prescribing information for NEXTSTELLIS includes a boxed warning for women ≥35 years who are smokers.6 This is consistent with product labeling for combined hormonal contraceptives.
In the Phase III clinical studies of NEXTSTELLIS, with a combined safety population of 3,632, a VTE occurred in 1 patient in the EU/Russian trial, for an annual incidence rate of 3.66 per 10,000 women-years.6,25 The annual risk for VTE in women on any COC is estimated at 3 to 9 per 10,000 women. Longer-term studies will be needed to determine if there are differences in VTE risk with NEXTSTELLIS compared with any other COC.

NEXTSTELLIS shares the same prescribing considerations as other estrogen-containing birth control pills.6,26 For more information, please see the full Prescribing Information.

Patients new to hormonal birth control can start NEXTSTELLIS on the first day of the menstrual cycle. Patients transitioning from other hormonal birth control methods can begin taking NEXTSTELLIS the day after stopping the previous method, or the next menstrual cycle.6
Get comprehensive information about starting patients on NEXTSTELLIS. A downloadable patient brochure guide is also available for patients starting NEXTSTELLIS.

IMPORTANT SAFETY INFORMATION FOR NEXTSTELLIS®

IMPORTANT SAFETY INFORMATION FOR NEXTSTELLIS® (drospirenone and estetrol tablets 3 mg/14.2 mg)

WARNING: CIGARETTE SMOKING AND SERIOUS CARDIOVASCULAR EVENTS

See full prescribing information for complete boxed warning.

  • Females over 35 years old who smoke should not use NEXTSTELLIS
  • Cigarette smoking increases the risk of serious cardiovascular events from combination oral contraceptive (COC) use.

 

HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use NEXTSTELLIS safely and effectively. See full prescribing information for NEXTSTELLIS.

NEXTSTELLIS (drospirenone and estetrol tablets), for oral use
Initial U.S. Approval: 2021

 

INDICATIONS AND USAGE

NEXTSTELLIS is a combination of drospirenone, a progestin, and estetrol, an estrogen, indicated for use by females of reproductive potential to prevent pregnancy.

 

LIMITATIONS OF USE

NEXTSTELLIS may be less effective in females with a BMI ≥30 kg/m2. In females with BMI ≥30 kg/m2, decreasing effectiveness may be associated with increasing BMI.

 

DOSAGE AND ADMINISTRATION

  • Take one tablet by mouth at the same time every day.
  • Take tablets in the order directed on the blister pack.

 

DOSAGE FORMS AND STRENGTHS

NEXTSTELLIS consists of 28 tablets in the following order:

  • 24 pink active tablets each containing drospirenone 3 mg and estetrol 14.2 mg
  • 4 white inert tablets

 

CONTRAINDICATIONS

  • A high risk of arterial or venous thrombotic diseases
  • Current or history of a hormonally-sensitive malignancy (e.g., breast cancer)
  • Hepatic adenoma, hepatocellular carcinoma, acute hepatitis or decompensated cirrhosis
  • Co-administration with hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir
  • Abnormal uterine bleeding that has an undiagnosed etiology
  • Renal impairment
  • Adrenal insufficiency

 

WARNINGS AND PRECAUTIONS

  • Thromboembolic Disorders and Other Vascular Problems: Stop NEXTSTELLIS if a thrombotic or thromboembolic event occurs. Start no earlier than 4 weeks after delivery. Consider all cardiovascular risk factors before initiating in any female, particularly in the presence of multiple risk factors.
  • Hyperkalemia: Check serum potassium concentration during the first NEXTSTELLIS treatment cycle in females on long-term treatment with medications that may increase serum potassium concentration.
  • Hypertension: Monitor blood pressure periodically and stop use if blood pressure rises significantly.
  • Migraine: Discontinue if new, recurrent, persistent, or severe migraines occur.
  • Hormonally-Sensitive Malignancy: Discontinue NEXTSTELLIS if a hormonally-sensitive malignancy is diagnosed.
  • Liver Disease: Withhold or permanently discontinue for persistent or significant elevation of liver enzymes.
  • Glucose Tolerance and Hypertriglyceridemia: Monitor glucose in females with prediabetes or diabetes. Consider an alternate contraceptive method for females with hypertriglyceridemia.
  • Gallbladder Disease and Cholestasis: Consider discontinuing NEXTSTELLIS in females with symptomatic gallbladder or cholestatic disease.
  • Bleeding Irregularities and Amenorrhea: May cause irregular bleeding or amenorrhea. Evaluate for other causes if symptoms persist.

 

ADVERSE REACTIONS

Most common adverse reactions (≥2%): Bleeding irregularities, mood disturbance, headache, breast symptoms, dysmenorrhea, acne, weight increased, and libido decreased

 

DRUG INTERACTIONS

  • CYP3A Inducers: May lead to contraceptive failure and/or increase breakthrough bleeding. Avoid concomitant use. If concomitant use is unavoidable, use an alternative or back-up contraceptive method during co-administration and up to 28 days after discontinuation of the CYP3A inducer.
  • See full Prescribing Information for additional clinically significant drug interactions.

 

USE IN SPECIFIC POPULATIONS

  • Pregnancy: Discontinue if pregnancy occurs.
  • Lactation: Advise postpartum females that NEXTSTELLIS can decrease milk production.

To report SUSPECTED ADVERSE REACTIONS, contact Mayne Pharma at 1-844-825-8500 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

See PATIENT COUNSELING INFORMATION and FDA-approved patient labeling.

BMI=body mass index; COC=combined oral contraceptive; EU=European Union; HDL=high-density lipoprotein; LDL=low-density lipoprotein; LNG=levonorgestrel.

 

 

REFERENCES
1. Coelingh Bennink HJT, Holinka CF, Diczfalusy E. Estetrol review: profile and potential clinical applications. Climacteric. 2008;11(suppl 1):47-58.
2. New data on NEXTSTELLIS presented at ISSWSH conference. News release. Mayne Pharma. Accessed May 21, 2021. https://www.maynepharma.com/investor-relations/company-announcements
3. Foidart JM, Gaspard U, Pequeux C, et al. Unique vascular benefits of estetrol, a native fetal estrogen with specific actions in tissues (NEST). In: Brinton RD, Genazzani AR, Simoncini T, Stevenson JC, eds. Sex Steroids’ Effects on Brain, Heart and Vessels Volume 6: Frontiers in Gynecological Endocrinology. New York, NY: Springer International Publishing; 2019:169‐195.
4. Blair R, Fang H, Branham WS, et al. The estrogen receptor relative binding affinities of 188 natural and xenochemicals: structural diversity of ligands. Toxicol Sci. 2000;54:138-153.
5. Mayne Pharma and Mithra announce FDA approval of new oral contraceptive NEXTSTELLIS®. News release. Mayne Pharma. Accessed May 21, 2021. https://www.maynepharma.com/media/2506/fda-approval-of-novel-oral-contraceptive-nextstellis.pdf
6. NEXTSTELLIS [package insert]. Raleigh, NC: Mayne Pharma; April 2021.
7. Arnal JF, Lenfant F, Metivier R, et al. Membrane and nuclear estrogen receptor alpha actions: from tissue specificity to medical implications. Physiol Rev. 2017;97(3):1045-1087.
8. Moggs JG, Orphanides G. Estrogen receptors: orchestrators of pleiotropic cellular responses. EMBO Rep. 2001;2(9):775-781.
9. Stanczyk FZ, Archer DF, Bhavnani BR. Ethinyl estradiol and 17β-estradiol in combined oral contraceptives: pharmacokinetics, pharmacodynamics and risk assessment. Contraception. 2013;87(6):706-727.
10. Food and Drug Administration. FDA label database. Accessed May 21, 2021. https://nctr-crs.fda.gov/fdalabel/ui/search
11. Abot A, Fontaine C, Buscato M, et al. The uterine and vascular actions of estetrol delineate a distinctive profile of estrogen receptor α modulation, uncoupling nuclear and membrane activation. EMBO Mol Med. 2014;6(10):1328-1346.
12. Ascenzi P, Bocedi A, Marino M. Structure-function relationship of estrogen receptor alpha and beta: impact on human health. Mol Aspects Med. 2006;27(4):299-402.
13. Coelingh Bennink HJT, Heegaard AM, Visser M, Holinka CF, Christiansen C. Oral bioavailability and bone-sparing effects of estetrol in an osteoporosis model. Climacteric. 2008;11(suppl 1):2-14.
14. Benoit T, Valera MC, Fontaine C, et al. Estetrol, a fetal selective estrogen receptor modulator, acts on the vagina of mice through nuclear estrogen receptor α activation. Am J Pathol. 2017;187(11):2499-2507.
15. Data on file. Clinical study report MIT‐Es0001‐C302. Mayne Pharma US. Raleigh, NC.
16. Szarewski A, Mansour D, Shulman LP. 50 years of “The Pill”: celebrating a golden anniversary. J Fam Plann Reprod Health Care. 2010;36(4):231-238.
17. Apter, D, Zimmerman Y, Beekman L, et al. Bleeding pattern and cycle control with estetrol-containing combined oral contraceptives: results from a phase II, randomised, dose-finding study (FIESTA). Contraception. 2016;94(4):366-373.
18. Data on file. Clinical study report MIT‐Es0001‐C201. Mayne Pharma US. Raleigh, NC.
19. Data on file. Clinical study report MIT‐Es0001‐C202. Mayne Pharma US. Raleigh, NC.
20. Data on file. Clinical study report ES-C01/PR3095. Mayne Pharma US. Raleigh, NC.
21. Data on file. Clinical study report ES-C02. Mayne Pharma US. Raleigh, NC
22. Visser M, Foidart JM, Coelingh Bennink JT. In vitro effects of estetrol on receptor binding, drug targets, and human liver cell metabolism. Climacteric. 2008;11(suppl 1):64-68.
23. Holinka CF, Gurpide E. In vivo effects of estetrol on the immature rat uterus. Biology of Reproduction. 1979;20:242-246.
24. Coelingh Bennink HJT, Verhoeven C, Zimmerman Y. Pharmacokinetics of the fetal estrogen estetrol in a multiple-rising-dose study in postmenopausal women. Climacteric. 2017;20(3):285-289
25. Data on file. NEXTSTELLIS New Drug Application, Module 2.5: Clinical Overview. Mayne Pharma US. Raleigh, NC.
26. Food and Drug Administration. Labeling for combined hormonal contraceptives: guidance for industry. Accessed May 11, 2021. https://www.fda.gov/media/110050/download