With NEXTSTELLIS®, your patients get the contraceptive efficacy they need, with the tolerability they want

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NEXTSTELLIS - combined to be native,
selective, and effective1-5

NEXTSTELLIS is the first ever oral contraceptive to combine estetrol (E4) with drospirenone (DSRP)2

  • DSRP has proven anti-androgenic and anti-mineralocorticoid properties6
  • Long half-lives: E4: 24h-28h7,8 – DSRP ~ 30h9

NEXTSTELLIS has been specifically designed to help overcome the issues associated with synthetic or modified estrogen-based COCs10

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NATIVE

  • E4 is a native estrogen, circulating at high levels in the mother and fetus during human pregnancy3
  • When used in NEXTSTELLIS, E4 is produced from a plant source4
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SELECTIVE

  • E4 is a selective estrogen that works differently than all other estrogens1,10-12
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EFFECTIVE

  • NEXTSTELLIS has 98% contraceptive efficacy in preventing pregnancy (Pearl Index of 2.65)2,5
  • Short hormone-free interval with a 24/4 monophasic regimen2,5

E4 will completely change how you think
about estrogen

ORGAN IMPACT MECHANISM OF ACTION OUTCOME

ENDOMETRIUM

HIGH Estrogen receptor (ER) agonist Good cycle control*

LIVER

NEUTRAL
  • Not metabolized by CYP450
  • ER mixed antagonist/agonist
Minimal to no impact on:
Cholesterol**
Triglycerides**
Glucose**
Clotting factors
Sex Hormone Binding Globulin (SHBG)

BREAST

LOW ER antagonist Inhibits estradiol-induced proliferation

*Studied paired with a progestin

**Compared at baseline, cycle 7, and cycle 14 in Phase 3 study

  • E4 has LOWER potency and binding affinity than that of E2 (which is less than EE) – so E4 is dosed in mg not mcg2,13
  • Unlike other estrogens, E4 has different actions in different tissues1,5,11,14
  • E4 provides the usual estrogen benefits to the vascular system, bone, vagina, and brain7,8,11,13,15-18
  • E4 is metabolized by the UGT2B7 system, found throughout the body8,9
    UGT, UDP-glycosyltransferase

What could all this mean for women taking NEXTSTELLIS?

1. NEXTSTELLIS efficacy is proven in a diverse population

  • NEXTSTELLIS has 98% contraceptive efficacy in preventing pregnancy (Pearl Index of 2.65)2,5
  • Short hormone-free interval with a 24/4 monophasic regimen2,5
  • Proven in large, robust Phase III clinical trials involving 3,632 women observed for >26,000 cycles2,5
    • Women 16-50 years (safety population)
    • 22% of women having a BMI 30-35 kg/m2
    • Diverse in ethnicity and race

2. NEXTSTELLIS delivers a predictable
bleeding profile2,5

% of women experiencing unscheduled mixed bleeding/spotting* or bleeding with NEXTSTELLIS (N=1,864)5**

% of women experiencing unscheduled mixed bleeding/spotting or bleeding with NEXTSTELLIS

  • Less than 2% of women experienced unscheduled bleeding5
  • The low rate of unscheduled bleeding starts at cycle 1 – with <1 day of unscheduled spotting or bleeding after cycle 15
  • Only 2.8% of women withdrew from treatment due to bleeding irregularities2

* Spotting was defined as minimal bleeding that did not require the use of any sanitary protection (including panty liners)
** Bleeding diaries were available for 1,758 patients at Cycle 1

3. NEXTSTELLIS also provides good tolerability ...2

Proven tolerability and safety in 2 Phase III studies with 3,632 patients studied over 26,455 cycles2

% of women experiencing adverse events (N=3632)2*

Weight gain 3%

Acne 3.7%

Mood 9.1%

Libido loss/ reduction 2%

Breast symptoms 5.4%

  • ONE venous thromboembolism (VTE) in the Phase III study program2
    Equates to 3.66 per 10,000 women-years2
  • Four Phase II trials, including two studies comparing NEXTSTELLIS to Yaz® and Nordette® – endpoints included ovulation inhibition, bleeding pattern, metabolic, endocrine and coagulation parameters5,19,20

*Any adverse reaction equals any adverse event ≥2%, non-drug related and drug related2

4. … with a very low incidence of treatment discontinuation2

9.6% of women discontinued NEXTSTELLIS due to adverse events2,5

9.6% of women discontinued NEXTSTELLIS due to adverse events

For your convenience, you can download NEXTSTELLIS summary information:

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. 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.
2. NEXTSTELLIS [package insert]. Raleigh, NC: Mayne Pharma; July 2022
3. Coelingh Bennink HJT, Holinka CF, Diczfalusy E. Estetrol review: profile and potential clinical applications. Climacteric. 2008;11(suppl 1):47-58.
4. Gerard C, Arnal J-F, Jost M et al. Profile of estetrol, a promising native estrogen for oral contraception and the relief of climacteric symptoms of menopause. Expert Rev. Clin. Pharmacol. 2022;15:121-137.
5. Data on file. Clinical study report MIT-Es0001-C302. Mayne Pharma US. Raleigh, NC.
6. Regidor PA, Schindler A. Antiandrogenic and antimineralocorticoid health benefits of COC containing newer progestogens: dienogest and drospirenone. Oncotarget. 2017;8(47):83334-83342.
7. Data on file. Clinical study report MIT-Es0001-C103. Mayne Pharma US. Raleigh, NC.
8. Visser M, Holinka CF, Coelingh Bennink HJT. First human exposure to exogenous single-dose oral estetrol in early postmenopausal women. Climacteric. 2008;11(suppl 1):31-40.
9. Blode H, Kowal K, Roth K, Reif S. Pharmacokinetics of drospirenone and ethinyl estradiol in Caucasian and Japanese women. Eur J Contracept Reprod Health Care. 2012;17(4):284-297.
10. Stanczyk FZ, Archer DF, Bhavnani BR. Ethinyl estradiol and 17ß-estradiol in combined oral contraceptives: pharmacokinetics, pharmacodynamics and risk assessment. Contraception. 2013;87(6):706-727.
11. 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.
12. Food and Drug Administration. FDA label database. Accessed May 21, 2021. https://nctr-crs.fda. gov/fdalabel/ui/search
13. Abot A, Fontaine C, Buscato M, et al. The uterine and vascular actions of estetrol delineate a distinctive profile of estrogen receptor a modulation, uncoupling nuclear and membrane activation. EMBO Mol Med. 2014;6(10):1328-1346.
14. Moggs JG, Orphanides G. Estrogen receptors: orchestrators of pleiotropic cellular responses. EMBO Rep. 2001;2(9):775-781.
15. Giretti MS et al. Effects of Estetrol on Migration and Invasion in T47-D Breast Cancer Cells through the Actin Cytoskeleton. Front Endocrinol 2014; 5: 80.
16. 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.
17. 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.
18. 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 a activation. Am J Pathol. 2017;187(11):2499-2507.
19. Data on file. Clinical study report MIT-Es0001-C201. Mayne Pharma US. Raleigh, NC.
20. Data on file. Clinical study report MIT-Es0001-C202. Mayne Pharma US. Raleigh, NC.