This portion of the website is intended for Healthcare Professionals.

Dosing and how to start a patient on NEXTSTELLIS®

NEXTSTELLIS offers product features that may appeal to patients at any point along their reproductive health journey. Whether your patients are considering birth control for the first time, switching to a better match for the long-term, or looking for flexible solutions to space their families, NEXTSTELLIS could be what’s NEXT for them.

What’s NEXT for your patient?

With NEXTSTELLIS, offer a 24/4 monophasic pill that fits in their plans1

“Starter”

Using contraception for the first time

For young adults or those new to hormonal contraception, starting the pill can seem like a big step. Patients may be reassured by learning more about the selective, targeted way NEXTSTELLIS works in the body.1,6

Starting a Patient on NEXTSTELLIS

“Switcher”

Wants to switch contraceptive methods

Patients interested in changing birth control methods may find it helpful to learn how the estrogen in NEXTSTELLIS compares with other combined hormone pills. If a patient has concerns about the estrogen in birth control, getting answers about estetrol and how NEXTSTELLIS is different may provide important context to support their decision.

Switching From Another Method

“Spacer”

Not yet ready to expand her family

Patients who are still growing their families may want to know how long after stopping NEXTSTELLIS they can expect to return to fertility. This was a secondary objective of a Phase II clinical trial of NEXTSTELLIS. On average, patients in the study resumed ovulation 17 days after stopping NEXTSTELLIS.32 Your “spacer” patients may find it helpful to know that NEXTSTELLIS is easy to start and stop and that there are data supporting a timetable for their return to fertility.

Starting a Postpartum Patient

“Perimenopausal”

Later in her reproductive life

Considerations for birth control may be more complex for patients later in their reproductive life. These patients may appreciate the metabolic profile of NEXTSTELLIS, which has been shown to have low impact on measures of lipid and glucose metabolism.7

Resource for patient counseling

Your patients have questions such as:

  • What makes NEXTSTELLIS different from other birth control pills?
  • How will it affect my period?
  • What are the side effects?

Help answer these questions and more with this downloadable patient brochure.

Instructions for starting or switching NEXTSTELLIS

To prevent pregnancy, patients should be instructed to take NEXTSTELLIS exactly as prescribed; 1 tablet daily for 28 consecutive days; 1 pink (active) tablet daily during the first 24 days and 1 white (inert) tablet daily during the following 4 days. Tablets must be taken every day at about the same time so that the interval between 2 tablets is always 24 hours.1 For patient instructions for starting NEXTSTELLIS and for missed pills, see the full Prescribing Information.

NEXTSTELLIS Dosing Packaging

No current hormonal method

Important:

  • In women with irregular menstrual cycles, pregnancy testing may be necessary before initiation of this product

Day 1 Start:

  • Take the first pink active tablet on the first day of menses
  • Take subsequent pink active tablets once daily at the same time each day for 24 days
  • Take 1 white inert tablet daily for 4 days and at the same time of day that active tablets were taken
  • Begin each subsequent 28-day pack on the same day of the week as the first cycle pack (i.e., on the day after taking the last tablet)

If not starting on the first day of menses, use a nonhormonal contraceptive (e.g., condoms and/or spermicide) as backup until 1 active tablet has been taken daily for 7 days in a row.

Combined hormonal pill

  • Start NEXTSTELLIS on the day when the new pack of the previous COC would have started

Progestin-only pill

  • Start NEXTSTELLIS the day after the last tablet was taken

Transdermal patch, vaginal insert,
or injection

  • Start NEXTSTELLIS on the day when the next application, insertion, or injection would have been scheduled

IUD or implant

  • Start NEXTSTELLIS on the day of removal

After pregnancy

Starting NEXTSTELLIS after delivery (>20 weeks gestation)

  • Must not start earlier than 4 weeks after delivery (due to increased risk for thromboembolism)
  • If menstrual cycles have returned, follow instructions for “Starting NEXTSTELLIS in females with no current use of hormonal contraception”
  • If menstrual cycles have not resumed, consider the possibility of ovulation and pregnancy. If not pregnant, use additional nonhormonal contraception for the first 7 days of NEXTSTELLIS use

Starting NEXTSTELLIS after abortion or miscarriage

If ≤14 weeks gestation

  • Within the first 7 days of complete first trimester abortion or miscarriage, use additional nonhormonal contraception for the next 7 days
  • After the first 7 days, follow instructions for “Starting NEXTSTELLIS in females with no current use of hormonal contraception”

If >14 weeks but ≤20 weeks gestation

  • After 4 weeks following second trimester abortion or miscarriage. Consider duration of pregnancy and increased risk for thromboembolism
  • If menstrual cycles have returned, follow instructions for “Starting NEXTSTELLIS in females with no current use of hormonal contraception”
  • If menstrual cycles have not resumed, consider the possibility of ovulation and pregnancy. If not pregnant, use additional nonhormonal contraception for the first 7 days of NEXTSTELLIS use
  • No current hormonal method

    Important:

    • In women with irregular menstrual cycles, pregnancy testing may be necessary before initiation of this product

    Day 1 Start:

    • Take the first pink active tablet on the first day of menses
    • Take subsequent pink active tablets once daily at the same time each day for 24 days
    • Take 1 white inert tablet daily for 4 days and at the same time of day that active tablets were taken
    • Begin each subsequent 28-day pack on the same day of the week as the first cycle pack (i.e., on the day after taking the last tablet)

    If not starting on the first day of menses, use a nonhormonal contraceptive (e.g., condoms and/or spermicide) as backup until 1 active tablet has been taken daily for 7 days in a row.

  • Combined hormonal pill
    • Start NEXTSTELLIS on the day when the new pack of the previous COC would have started
  • Progestin-only pill
    • Start NEXTSTELLIS the day after the last tablet was taken
  • Transdermal patch, vaginal insert, or injection
    • Start NEXTSTELLIS on the day when the next application, insertion, or injection would have been scheduled
  • IUD or implant
    • Start NEXTSTELLIS on the day of removal
  • After pregnancy

    Starting NEXTSTELLIS after delivery (>20 weeks gestation)

    • Must not start earlier than 4 weeks after delivery (due to increased risk for thromboembolism)
    • If menstrual cycles have returned, follow instructions for “Starting NEXTSTELLIS in females with no current use of hormonal contraception”
    • If menstrual cycles have not resumed, consider the possibility of ovulation and pregnancy. If not pregnant, use additional nonhormonal contraception for the first 7 days of NEXTSTELLIS use

    Starting NEXTSTELLIS after abortion or miscarriage

    If ≤14 weeks gestation

    • Within the first 7 days of complete first trimester abortion or miscarriage, use additional nonhormonal contraception for the next 7 days
    • After the first 7 days, follow instructions for “Starting NEXTSTELLIS in females with no current use of hormonal contraception”

    If >14 weeks but ≤20 weeks gestation

    • After 4 weeks following second trimester abortion or miscarriage. Consider duration of pregnancy and increased risk for thromboembolism
    • If menstrual cycles have returned, follow instructions for “Starting NEXTSTELLIS in females with no current use of hormonal contraception”
    • If menstrual cycles have not resumed, consider the possibility of ovulation and pregnancy. If not pregnant, use additional nonhormonal contraception for the first 7 days of NEXTSTELLIS use

IMPORTANT SAFETY INFORMATION

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.

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

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.

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.

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. NEXTSTELLIS [package insert]. Greenville, NC: Mayne Pharma; April 2021. 2. 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. 3. Hall KS, Trussell J. Types of combined oral contraceptives used by U.S. women. Contraception. 2012;86(6):659-665. 4. Coelingh Bennink HJT, Holinka CF, Diczfalusy E. Estetrol review: profile and potential clinical applications. Climacteric. 2008;11(suppl 1):47-58. 5. New data on NEXTSTELLIS presented at ISSWSH conference. News release. Mayne Pharma. Accessed May 21, 2021. https://www.maynepharma.com/investor-relations/company-announcements 6. 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. 7. Data on file. Clinical study report MIT‐Es0001‐C302. Mayne Pharma US. Greenville, NC. 8. Data on file. Clinical study report MIT‐Es0001‐C201. Mayne Pharma US. Greenville, NC. 9. 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. 10. Moggs JG, Orphanides G. Estrogen receptors: orchestrators of pleiotropic cellular responses. EMBO Rep. 2001;2(9):775-781. 11. 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. 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 α modulation, uncoupling nuclear and membrane activation. EMBO Mol Med. 2014;6(10):1328-1346. 14. 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. 15. 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. 16. 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. 17. Shoham Z, Kopernik G. Tools for making correct decisions regarding hormone therapy. Part I: background and drugs. Fertil Steril. 2004;81(6):1447-1457. 18. 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. 19. 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. 20. Data on file. Clinical study report MIT‐Es0001‐C103. Mayne Pharma US. Greenville, NC. 21. 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. 22. 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. 23. Regidor PA, Schindler A. Antiandrogenic and antimineralocorticoid health benefits of COC containing newer progestogens: dienogest and drospirenone. Oncotarget. 2017;8(47):83334-83342. 24. 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. 25. Levy T, Yairi Y, Bar-Hava I, et al. Pharmacokinetics of the progesterone-containing vaginal tablet and its use in assisted reproduction. Steroids. 2000;65(10-11):645-649. 26. Kuhl H. Pharmacology of estrogens and progestogens: influence of different routes of administration. Climacteric. 2005;8(suppl 1):3-63. 27. Ortho Tri-Cyclen [package insert]. Titusville, NJ: Janssen Pharmaceuticals Inc; October 2013. 28. Aygestin [package insert]. Pomona, NY: Duramed Pharmaceuticals Inc; July 2007. 29. Data on file. Clinical study report MIT‐Es0001‐C301. Mayne Pharma US. Greenville, NC. 30. Data on file. Clinical study report MIT‐Es0001‐C202. Mayne Pharma US. Greenville, NC. 31. Food and Drug Administration. Prescription and over-the-counter drug product list: additions/deletions for prescription drug product list. August 2015. Accessed May 21, 2021. https://www.fda.gov/media/93516/download 32. Data on file. Clinical study report ES-C01/PR3095. Mayne Pharma US. Greenville, NC. 33. Data on file. Clinical study report ES-C02. Mayne Pharma US. Greenville, NC. 34. 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 35. Electronic Code of Federal Regulations. IND safety reporting. 21 CFR §312.32. Accessed May 21, 2021. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=312.32 36. Data on file. NEXTSTELLIS New Drug Application, Module 2.5: Clinical Overview. Mayne Pharma US. Greenville, NC. 37. Holinka CF, Gurpide E. In vivo effects of estetrol on the immature rat uterus. Biology of Reproduction. 1979;20:242-246. 38. 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. 39. Food and Drug Administration. Labeling for combined hormonal contraceptives: guidance for industry. Accessed May 11, 2021. https://www.fda.gov/media/110050/download