Product Overview
π First & only FDA-approved oral contraceptive containing estetrol (E4) β the first new estrogen in over 50 years.
| Attribute | Detail |
|---|---|
| Brand Name | NEXTSTELLIS |
| Generic Name | Drospirenone 3 mg / Estetrol 14.2 mg |
| NDA Number | 214154 |
| FDA Approval | April 15, 2021 |
| Dosage Form | Oral tablet β 24 active pink tablets + 4 inert white tablets (28-day cycle) |
| Route | Oral, once daily |
β
FDA-APPROVED INDICATION: NEXTSTELLIS is indicated for use by females of reproductive potential to prevent pregnancy. β PI Section 1
Mechanism of Action
NEXTSTELLIS combines two active components with distinct pharmacological profiles working synergistically for effective ovulation suppression.
Estetrol (E4) β Novel Native Estrogen
1
Naturally Occurring Estrogen
Estetrol is a native estrogen produced only during human pregnancy by the fetal liver. It is the first novel estrogen to be used in a COC in over 50 years, replacing ethinyl estradiol (EE) which has been the standard since the 1960s.
2
Selective Nuclear ERΞ± Activation
E4 activates nuclear estrogen receptor-Ξ± (ERΞ±) signaling β the classical genomic pathway responsible for endometrial stabilization and gonadotropin suppression. This provides effective ovulation inhibition.
3
Minimal Membrane ERΞ± Activation
Unlike EE, E4 does NOT significantly activate membrane ERΞ± in specific tissues. Membrane ERΞ± activation is associated with hepatic effects (SHBG production, clotting factor changes). This tissue-selective profile may contribute to a differentiated safety profile.
4
Lower Hepatic Impact
Due to its selective receptor activation pattern, E4 has demonstrated lower impact on liver-derived proteins compared to EE in preclinical and clinical studies, potentially offering a more favorable cardiovascular and metabolic profile.
β
FDA-APPROVED LANGUAGE: "Estetrol is an estrogen. The progestational activity of NEXTSTELLIS is mainly due to drospirenone." β PI Section 12.1
Drospirenone (DRSP) β Progestin Component
- Anti-mineralocorticoid activity: counteracts estrogen-induced water retention
- Anti-androgenic activity: blocks testosterone receptor binding
- No estrogenic, androgenic, or glucocorticoid activity
- Combined with E4, provides effective ovulation suppression and endometrial stabilization
β οΈ SAFETY β Hyperkalemia Risk: DRSP has anti-mineralocorticoid activity. Contraindicated in renal impairment, hepatic impairment, and adrenal insufficiency. Monitor serum potassium in patients taking potassium-sparing diuretics, ACE inhibitors, ARBs, or NSAIDs. β PI Section 5.2
Pivotal Clinical Trial Data
Phase III Study Design
| Parameter | Detail |
|---|---|
| Population | 3,725 women aged 16β50 years |
| Design | Open-label, multicenter |
| Duration | 13 cycles (1 year) |
| Primary Endpoint | Pearl Index (pregnancies per 100 woman-years) |
| Key Secondary | Bleeding pattern, cycle control, safety |
Efficacy Results
| Endpoint | Result | Clinical Significance |
|---|---|---|
| 13-Cycle Pearl Index (US, 16-35 yrs) | 2.65 | Comparable to other COCs in typical clinical trial settings |
| 13-Cycle Life-table Pregnancy Rate | 2.1% | Within expected range for combined hormonal contraceptives |
| Scheduled Bleeding (per cycle) | 82.9β87.0% | Predictable cycle control |
| Median Bleeding Duration | 4.5 days | Manageable bleeding days |
| Unscheduled Bleeding (Cycle 1β4) | 30.3% β 21.3% | Decreasing trend over time β reassure patients |
β
KEY EFFICACY DATA (Per PI): The primary efficacy endpoint was the Pearl Index. The PI for US women 16β35 was 2.65 pregnancies per 100 woman-years. Counsel patients on typical-use vs. perfect-use efficacy rates.
Safety Profile β Complete ISI Summary
β οΈ BOXED WARNING AREA β Cigarette Smoking: Females β₯35 years who smoke are CONTRAINDICATED. Cigarette smoking increases the risk of serious cardiovascular events from combined hormonal contraceptive use. β PI Boxed Warning
Contraindications (PI Section 4)
- High risk of arterial or venous thrombotic disease
- Liver tumors or hepatic disease
- Undiagnosed abnormal uterine bleeding
- Breast cancer or other hormone-sensitive cancer (current or history)
- Renal impairment (all severities)
- Adrenal insufficiency
- Use of Hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir
- Smokers β₯35 years of age
Most Common Adverse Reactions (β₯2%)
| Adverse Reaction | Incidence |
|---|---|
| Bleeding irregularities (includes metrorrhagia) | Variable by cycle |
| Mood disturbance (depression, mood swings) | 10.9% |
| Breast symptoms (tenderness, pain) | 5.3% |
| Headache | 4.8% |
| Dysmenorrhea | 3.0% |
| Acne | 2.8% |
| Weight gain | 2.5% |
| Decreased libido | 2.2% |
Competitive Landscape (Compliance-Safe Framing)
β οΈ COMPLIANCE ALERT: All competitive comparisons below use ONLY published data from FDA labels and peer-reviewed sources. Speakers must not make unsubstantiated superiority claims. Indirect comparisons require caveats. 21 CFR 202.1
Oral Contraceptive Comparison
| Feature | NEXTSTELLIS | Yaz (Bayer) | Lo Loestrin Fe | NuvaRing |
|---|---|---|---|---|
| Estrogen | Estetrol (novel) | Ethinyl estradiol 20ΞΌg | Ethinyl estradiol 10ΞΌg | Ethinyl estradiol 15ΞΌg |
| Progestin | Drospirenone 3mg | Drospirenone 3mg | Norethindrone 1mg | Etonogestrel |
| Regimen | 24/4 oral | 24/4 oral | 24/2/2 oral | 21 in / 7 out ring |
| Delivery | Oral tablet | Oral tablet | Oral tablet | Vaginal ring |
| Novel MOA | Tissue-selective ERΞ± | Standard ERΞ± | Standard ERΞ± | Standard ERΞ± |
| Generic Available | No (brand only) | Yes (multiple) | Yes | Yes |
| Approval Year | 2021 | 2006 | 2010 | 2001 |
π KEY DIFFERENTIATOR: NEXTSTELLIS is the ONLY OC with estetrol β a novel estrogen with tissue-selective ERΞ± activation. This is a factual, PI-based differentiator that speakers can state without comparative efficacy/safety claims.
Patient Case Studies
Review 5 clinical scenarios and select the most appropriate management approach. Each case includes compliance-aligned decision points.
Case 1 of 5
Objection Handling Simulator
Practice responding to common HCP questions and objections with compliance-safe answers. Select the best response for each scenario β your compliance score is tracked.
Compliant β
Green highlight
Green highlight
Non-Compliant β
Red highlight
Red highlight
Compliance Scenario Training
Navigate real-world compliance scenarios that may arise during speaker programs. Select the correct course of action.
Knowledge Assessment
Test your understanding of NEXTSTELLIS product knowledge, safety information, and compliance requirements. Answer all questions to see your score.