NEXTSTELLIS® (DRSP/E4) clinical trial program overview

NEXTSTELLIS is proven through a robust research program in women that included a range of age, BMI, and racial diversity1-5

View the NEXTSTELLIS results delivered against key endpoints in a large, multi-phase clinical trial program1-5

Phase II

4 trials

681 patients

Phase III

2 trials

3,632 patients

NEXTSTELLIS demonstrated efficacy and safety in a robust clinical trial program.
The Phase III patient population included women 16 to 50 years of age and a high-BMI cohort (22% of patients had BMI 30-35 kg/m2).1-3

NEXTSTELLIS head-to-head comparison against Yaz® and Nordette®1,2,4,5

In 2 Phase II safety studies, NEXTSTELLIS was studied head-to-head against 2 standard-of-care COCs*:

  • Yaz® (20 mcg EE/3 mg DRSP)
  • Nordette®** (30 mcg EE/150 mcg LNG)

Endpoints included4,5:

  • Hemostasis parameters
  • Endocrine parameters, as well as SHBG
  • Lipid and carbohydrate metabolism parameters
  • Ovulation inhibition

*Both Phase II studies included Yaz® (EE/DRSP) as a comparator; only 1 (C201) included Nordette® (EE/LNG)

**European trade name is Melleva®6

Phase III trial program

Patient demographics reflect a real-world range in age (16-50 years of age), ethnicity, weight, and contraceptive history1-3

NEXTSTELLIS Phase III trial program

The 2 Phase III trials of NEXTSTELLIS studied 3,632 women (ages 16-50 years). The efficacy population in the North American trial was 1,524 (ages 16-35 years), and in the EU/Russian study, it was 1,313 (ages 18-35 years). Women were studied over 12 months for 13 menstrual cycles, totaling 26,455 at-risk cycles.1-3

Patient demographics


  • Switching: 42%
  • Starting: 58%
  • Naive users: 17%


  • 22% had BMI 30-35 kg/m2 (mean BMI: 25.8 kg/m2)


  • Hispanic or Latino: 26%
  • Not Hispanic or Latino: 74%


  • White: 70%
  • Black: 20%
  • Asian: 5%
  • American Indian or Alaskan Native: 1%
  • Native Hawaiian or Pacific Islander: 0.4%
  • Other: 4%

Phase III data: Results from a large and
inclusive trial program

Contraceptive efficacy


NEXTSTELLIS was 98% effective in preventing pregnancy (Pearl index: 2.65).1,2

Effective across a range of body weights


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.1

NEXTSTELLIS delivered bleeding patterns that were similar to a natural predictable menstrual cycle2

NEXTSTELLIS, with its 24/4 monophasic regimen, delivers a predictable bleeding pattern1,2

Scheduled Bleeding


On average, 85% of women experienced regular withdrawal bleeding (range: 82%-87% across cycles). Average duration was 4.5 days2

Unscheduled Bleeding


<2% of patients experienced unscheduled bleeding-only episodes after cycle 22

Average Duration

<1 day

<1 day of any unscheduled spotting or bleeding on average per cycle after cycle 12

Treatment Discontinuation


2.8% of patients withdrew from treatment due to bleeding irregularities2


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


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.



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



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



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.



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



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



  • 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



  • 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.



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



  • 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.



  • 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

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.



1. NEXTSTELLIS [package insert]. Raleigh, NC: Mayne Pharma; April 2021.
2. Data on file. Clinical study report MIT‐Es0001‐C302. Mayne Pharma US. Raleigh, NC.
3. Data on file. Clinical study report MIT‐Es0001‐C301. Mayne Pharma US. Raleigh, NC.
4. Data on file. Clinical study report MIT‐Es0001‐C201. Mayne Pharma US. Raleigh, NC.
5. Data on file. Clinical study report MIT‐Es0001‐C202. Mayne Pharma US. Raleigh, NC.
6. Data on file. Clinical study report MIT‐Es0001‐C202. Mayne Pharma US. Raleigh, NC.
7. 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.