DROSPIRENONE, ETHINYL ESTRADIOL AND LEVOMEFOLATE CALCIUM Drug Patent Profile

When do Drospirenone, Ethinyl Estradiol And Levomefolate Calcium patents expire, and what generic alternatives are available?

Drospirenone, Ethinyl Estradiol And Levomefolate Calcium is a drug marketed by Lupin and Watson Labs Inc and is included in three NDAs.

The generic ingredient in DROSPIRENONE, ETHINYL ESTRADIOL AND LEVOMEFOLATE CALCIUM is drospirenone; ethinyl estradiol; levomefolate calcium. There is one drug master file entry for this compound. Three suppliers are listed for this compound. Additional details are available on the drospirenone; ethinyl estradiol; levomefolate calcium profile page.

Summary for DROSPIRENONE, ETHINYL ESTRADIOL AND LEVOMEFOLATE CALCIUM

US Patents:	0
Applicants:	2
NDAs:	3
Finished Product Suppliers / Packagers:	1
Clinical Trials:	1
DailyMed Link:	DROSPIRENONE, ETHINYL ESTRADIOL AND LEVOMEFOLATE CALCIUM at DailyMed

Recent Clinical Trials for DROSPIRENONE, ETHINYL ESTRADIOL AND LEVOMEFOLATE CALCIUM

Identify potential brand extensions & 505(b)(2) entrants

Sponsor	Phase
Bayer	Phase 3

See all DROSPIRENONE, ETHINYL ESTRADIOL AND LEVOMEFOLATE CALCIUM clinical trials

US Patents and Regulatory Information for DROSPIRENONE, ETHINYL ESTRADIOL AND LEVOMEFOLATE CALCIUM

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Exclusivity Expiration
Lupin	DROSPIRENONE, ETHINYL ESTRADIOL AND LEVOMEFOLATE CALCIUM	drospirenone; ethinyl estradiol; levomefolate calcium	TABLET;ORAL	205947-001	Jun 13, 2018	AB	RX	No	No
Watson Labs Inc	DROSPIRENONE, ETHINYL ESTRADIOL AND LEVOMEFOLATE CALCIUM	drospirenone; ethinyl estradiol; levomefolate calcium	TABLET;ORAL	203593-001	Oct 11, 2016	AB	RX	No	No
Watson Labs Inc	DROSPIRENONE, ETHINYL ESTRADIOL AND LEVOMEFOLATE CALCIUM	drospirenone; ethinyl estradiol; levomefolate calcium	TABLET;ORAL	203594-001	Oct 11, 2016	AB	RX	No	No

Drospirenone, Ethinyl Estradiol and Levomefolate Calcium Market Dynamics, Patent Position and Financial Trajectory

Last updated: August 29, 2026

Drospirenone, ethinyl estradiol and levomefolate calcium is a mature combined oral contraceptive combination with stable clinical demand, limited differentiation and substantial generic-price pressure. The principal branded products are Beyaz and Safyral, both associated with Bayer. The combination has largely moved from an innovation-driven market to a mature, prescription-volume market in which access, payer coverage, generic substitution and retail pricing determine commercial performance.

Beyaz contains drospirenone 3 mg, ethinyl estradiol 0.02 mg and levomefolate calcium 0.451 mg. Safyral contains drospirenone 3 mg, ethinyl estradiol 0.03 mg and levomefolate calcium 0.451 mg. The products use a 24-day or 21-day hormonal regimen, respectively, with folate-containing tablets in the treatment cycle. The combination is approved for contraception. Beyaz also has labeling for premenstrual dysphoric disorder and moderate acne in appropriate patients [1][2].

What is the commercial market for drospirenone, ethinyl estradiol and levomefolate calcium?

The market is a mature oral contraceptive segment with recurring demand and limited product-level growth. Demand is supported by contraception, acne treatment and, for Beyaz, premenstrual dysphoric disorder. Growth is constrained by generic alternatives, low switching costs and the availability of other hormonal contraceptive methods.

Product	Hormonal dose	Folate dose	Primary commercial position	Manufacturer or sponsor
Beyaz	Drospirenone 3 mg / ethinyl estradiol 0.02 mg	0.451 mg	Brand low-estrogen formulation with PMDD and acne labeling	Bayer
Safyral	Drospirenone 3 mg / ethinyl estradiol 0.03 mg	0.451 mg	Brand higher-estrogen formulation	Bayer
Tydemy	Drospirenone 3 mg / ethinyl estradiol 0.03 mg	0.451 mg	Generic equivalent to the Safyral-type formulation	Lupin
Other generic equivalents	Primarily 0.02 mg or 0.03 mg ethinyl estradiol strengths	Varies by product	Low-price substitution	Multiple ANDA holders

The commercial value of levomefolate calcium is limited. Folate creates a formulation and labeling distinction, but it does not create a durable barrier against substitution by conventional drospirenone/ethinyl estradiol products. Physicians and patients may value folate supplementation, but payers generally evaluate the combination against lower-cost contraceptives.

What are the main revenue drivers for this contraceptive combination?

Revenue depends on prescription volume, brand retention, insurance coverage and the number of approved generic suppliers. Unit demand is relatively resilient because contraception is a recurring-use therapy. Revenue per prescription is less resilient because generic entry quickly reduces net pricing.

The principal commercial drivers are:

1. Continued use of oral contraception among reproductive-age patients.
2. Retention of Beyaz or equivalent products among patients seeking a drospirenone-based pill with folate.
3. Coverage decisions by commercial insurers and pharmacy benefit managers.
4. Availability of low-cost generic products.
5. Demand for drospirenone-based treatment in acne and PMDD populations.
6. Retail pharmacy substitution rules and prescriber use of dispense-as-written instructions.

Drospirenone also has a differentiated pharmacology compared with some older progestins. Its antimineralocorticoid activity can support a distinct clinical profile, but it also increases attention to potassium-related warnings and thromboembolic risk. The safety profile affects prescribing, patient selection and payer management [1][3].

What is the financial trajectory of Beyaz and Safyral?

The likely financial trajectory is declining branded revenue, followed by a lower but more stable generic market.

Bayer does not generally report standalone revenue for Beyaz or Safyral in its public financial statements. The products are not separately disclosed as material operating segments. Public reporting therefore supports directional analysis rather than a product-specific revenue series [4].

Brand phase

Before generic competition, Bayer could capture a premium for:

• The Beyaz folate formulation.
• The 24 active-pill regimen.
• PMDD and acne labeling.
• Brand recognition associated with Yaz and related products.
• Physician familiarity with drospirenone-containing oral contraceptives.

The premium was constrained by the availability of Yaz and generic drospirenone/ethinyl estradiol products without levomefolate calcium. Those products provided a clinically familiar substitute at a lower price.

Generic erosion phase

Generic entry reduced the addressable branded premium. Once multiple ANDA-approved suppliers entered the market, pharmacy substitution and payer controls shifted demand toward lower-cost equivalents. This normally produces:

• Rapid reduction in brand prescription share.
• Lower average selling price.
• Higher rebate requirements.
• Greater dependence on specialty retail positioning.
• Lower return on promotional spending.

Mature generic phase

The mature market is characterized by relatively stable volume and falling price. Manufacturers compete primarily on:

• Wholesale acquisition cost.
• Supply reliability.
• Pharmacy channel access.
• Contract pricing.
• Manufacturing cost.
• Ability to avoid recalls and back orders.

Standalone generic revenue is not publicly disclosed by most suppliers. Tydemy revenue is also not reported as a separate material line item by Lupin. The economic value is therefore best assessed through prescription volume, market share and net price rather than reported product sales.

When did this drug combination lose exclusivity?

The commercial exclusivity period ended after the relevant branded products had been exposed to generic competition. Beyaz received FDA approval in 2010, while Safyral also received FDA approval in 2010 [1][2]. Their commercial protection did not prevent later ANDA approvals for equivalent drospirenone, ethinyl estradiol and levomefolate calcium products.

For mature oral contraceptives, exclusivity is usually governed less by one decisive patent expiration date than by the combined effect of:

• Orange Book-listed patents.
• Patent-term calculations.
• Paragraph IV litigation.
• Regulatory exclusivity.
• Formulation and use patents.
• The timing of first ANDA approval.
• The number of subsequent generic entrants.

The relevant market has passed the high-value exclusivity stage. Current financial exposure is primarily generic price erosion rather than imminent loss of a large protected franchise.

What patents protect drospirenone, ethinyl estradiol and levomefolate calcium?

Protection for the combination historically could include patents covering:

• The combination of drospirenone and ethinyl estradiol.
• Specific estrogen concentrations.
• Regimen design, including active and inactive tablets.
• Levomefolate calcium inclusion.
• Treatment of PMDD or acne.
• Pharmaceutical compositions and packaging.
• Manufacturing or crystallization processes.

The original drospirenone and ethinyl estradiol composition patents were developed around Bayer’s oral contraceptive franchise, including Yasmin and Yaz. Later products such as Beyaz and Safyral added folate-related formulation and product distinctions. The practical strength of these rights declined as the core hormonal combination matured and generic applicants developed non-infringing or abbreviated regulatory pathways.

How strong is the patent estate?

The estate is commercially weak to moderate for the mature combination. It has historical value but limited ability to support premium pricing today.

Patent category	Historical value	Current commercial strength
Core drospirenone/ethinyl estradiol composition	High during initial launch period	Low after generic entry
Folate-containing formulation	Moderate	Limited if generic equivalence is established
PMDD method of use	Moderate for labeled positioning	Narrow and difficult to monetize broadly
Acne method of use	Moderate	Limited by competing therapies and generic substitutes
Manufacturing patents	Potentially meaningful	Relevant mainly to supply and cost structure
Packaging or regimen patents	Narrow	Usually low once alternative designs are available

A formulation patent can delay competition only if it is valid, enforceable and difficult to design around. Folate inclusion alone is unlikely to support a durable premium where the active hormonal components are widely available and multiple generic manufacturers can obtain approval.

What is the Orange Book status of Beyaz and Safyral?

Beyaz and Safyral were listed in the FDA’s Orange Book as approved prescription drug products. Orange Book analysis for these products requires reviewing the product-specific patent and exclusivity entries, not only the active ingredient name. The relevant record may differ by strength, dosage form, sponsor and approved product number [5].

The commercial significance of Orange Book listings is now limited because:

• The products are mature.
• Generic versions have reached the market.
• Any remaining listed rights must be evaluated for expiration, enforceability and scope.
• Generic applicants can challenge listed patents through Paragraph IV certifications.
• Later generic entrants may avoid earlier exclusivity advantages held by first filers.

Which companies are challenging or competing with the branded products?

The principal competitive threat comes from ANDA-based generic manufacturers rather than biosimilar developers. Known commercial competition includes Lupin’s Tydemy and other suppliers of drospirenone/ethinyl estradiol products, although product availability varies by country and over time.

Competition comes from four groups:

Generic oral contraceptive manufacturers

These companies compete directly on equivalent or closely related hormonal formulations. Their advantages are lower cost, payer acceptance and pharmacy substitution.

Manufacturers of drospirenone/ethinyl estradiol without levomefolate

Products such as generic Yaz-type formulations compete for patients who want drospirenone and ethinyl estradiol but do not require a folate-containing tablet.

Alternative combined oral contraceptives

Products using levonorgestrel, norethindrone, desogestrel or norgestimate compete for the same contraception market. Lower-cost products can displace drospirenone formulations where acne or PMDD is not a primary treatment objective.

Long-acting and nonoral contraception

Intrauterine systems, implants, injections, patches and vaginal rings compete for contraceptive demand. These products reduce the total addressable market for daily oral pills but do not directly replicate the acne and PMDD positioning of Beyaz.

Are biosimilars a risk for this product?

No. Biosimilar risk is not relevant because drospirenone, ethinyl estradiol and levomefolate calcium are chemically synthesized small molecules, not biologic medicines. Competition occurs through generic-drug pathways, principally ANDAs under Section 505(j) of the Federal Food, Drug, and Cosmetic Act [6].

The relevant regulatory risks are generic approval, therapeutic substitution, manufacturing compliance, product recalls and supply disruption.

What Paragraph IV challenges affect the combination?

Paragraph IV risk was most important when branded patents could delay ANDA approval or trigger patent litigation. A generic applicant files a Paragraph IV certification when it asserts that an Orange Book-listed patent is invalid, unenforceable or not infringed.

For this mature combination, Paragraph IV litigation has less financial significance than it had during the initial generic-entry period. The main commercial questions are now:

• Whether any listed patent remains unexpired.
• Whether a first applicant obtained 180-day generic exclusivity.
• Whether later ANDA applicants can enter after the first filer.
• Whether the generic product is therapeutically substitutable.
• Whether manufacturing capacity can support national distribution.

No active, high-value litigation outcome should be assumed solely from the historical existence of Beyaz or Safyral patents. Patent and court databases must be reviewed for product-specific litigation status before relying on an exclusivity date.

What formulation patents protect the product?

The formulation distinction is the addition of levomefolate calcium to a drospirenone/ethinyl estradiol oral contraceptive regimen. Potentially relevant claims can cover:

• The precise active-ingredient ratios.
• Tablet composition.
• Folate dosage.
• Separation of hormonal and folate tablets.
• Tablet sequence and regimen.
• Stability and dissolution characteristics.

The folate component improves product differentiation but does not materially change the underlying market structure. Generic manufacturers can compete through equivalent product development, alternative excipients or separate approved formulations, subject to FDA requirements.

What method-of-use patents protect Beyaz?

Beyaz’s commercial labeling includes contraception, PMDD and moderate acne indications in specified patient populations [1]. Method-of-use rights may have supported those positions historically, but their value is narrower than composition claims. Physicians can prescribe competing drospirenone/ethinyl estradiol products for overlapping clinical needs, and generics may enter with label carve-outs for protected uses where permitted.

PMDD and acne claims can support brand differentiation, but they are unlikely to preserve substantial revenue once the core contraceptive product is genericized.

What FDA regulatory issues affect the market?

The main FDA issues are bioequivalence, labeling, manufacturing quality and postmarketing safety.

Drospirenone-containing combined hormonal contraceptives carry warnings concerning venous thromboembolic risk and other contraindications. FDA labeling requires patient selection, risk assessment and adherence to contraindications [1][3].

Manufacturing failures can alter market share quickly. A recall or supply interruption can shift prescriptions to competing generics, but it can also create temporary shortages that support short-term pricing for manufacturers with available inventory. Lupin’s 2023 recall of certain Tydemy lots illustrates the operational risk associated with assay and quality-control issues [7].

What generic entry risks exist for the branded franchise?

The major risks are permanent rather than transitional:

• Generic substitution removes the brand premium.
• Multiple suppliers create price competition.
• Payers may exclude brand products.
• Contraceptive prescribing is sensitive to copay differences.
• Folate differentiation may not justify higher reimbursement.
• Alternative contraceptive methods limit pricing power.
• Recalls can damage supply reliability and patient retention.

The main residual opportunity is a small branded segment with patients or prescribers who prefer the original product, specific labeling or a particular regimen. That segment is unlikely to support historical brand economics.

How does the product compare with other drospirenone contraceptives?

Attribute	Beyaz	Safyral	Generic Yaz-type product	Tydemy
Drospirenone	3 mg	3 mg	3 mg	3 mg
Ethinyl estradiol	0.02 mg	0.03 mg	Usually 0.02 mg	0.03 mg
Levomefolate calcium	Yes	Yes	Usually no	Yes
PMDD labeling	Yes for Beyaz	Not equivalent to Beyaz labeling	Product-specific	Product-specific
Price position	Brand premium	Brand premium	Low-cost generic	Generic
Main commercial advantage	Low-estrogen and folate positioning	Folate and higher-estrogen formulation	Price	Price plus folate

What is the likely future financial trajectory?

The base case is stable or modestly declining prescription volume combined with continued net-price compression. The market should remain commercially viable for efficient generic manufacturers with reliable supply and competitive contracts. It is unlikely to return to the revenue profile associated with protected branded contraception.

Potential upside is limited to temporary supply shortages, improved payer positioning, niche brand retention or expansion into markets where generic penetration remains low. Downside risk comes from additional generic entrants, lower reimbursement, safety-related publicity and manufacturing recalls.

Key Takeaways

• Drospirenone, ethinyl estradiol and levomefolate calcium is a mature oral contraceptive combination.
• Beyaz and Safyral are the principal historical branded products associated with Bayer.
• Tydemy represents generic competition for the higher-estrogen folate-containing formulation.
• Levomefolate calcium differentiates the product but does not create a strong long-term commercial moat.
• Biosimilar risk does not apply; generic-drug competition is the relevant pathway.
• Brand revenue has likely undergone substantial erosion, while generic market volume remains recurring.
• Product-specific Orange Book and Paragraph IV analysis remains important for litigation and entry timing, but current value is concentrated in manufacturing efficiency, supply reliability and payer access.
• The long-term financial outlook is stable-to-declining revenue per prescription, not a return to high-margin exclusivity economics.

FAQs

Is levomefolate calcium clinically necessary in this contraceptive combination?

Levomefolate calcium is intended to increase folate levels in women using the contraceptive. It differentiates the formulation but is not required for the contraceptive effect of drospirenone and ethinyl estradiol.

Is Beyaz the same as Yaz?

No. Both contain drospirenone and ethinyl estradiol, but Beyaz adds levomefolate calcium and has distinct labeling. Beyaz also uses a lower ethinyl estradiol dose than some related products.

Can pharmacies automatically substitute a generic for Beyaz?

Substitution depends on the approved generic, state law, payer policy and the prescription instructions. A generic must meet FDA requirements for therapeutic equivalence to the reference product for substitution under applicable rules.

Does this drug combination have a patent-protected acne indication?

The product has acne-related labeling in specified patients, but a method-of-use claim does not necessarily prevent generic entry for contraception. Generic applicants may use regulatory mechanisms such as label carve-outs where applicable.

What is the largest commercial risk for generic manufacturers?

The largest risk is usually manufacturing and supply reliability. In a price-sensitive contraceptive market, a recall, failed inspection or shortage can cause rapid loss of pharmacy and payer business.

References

1. U.S. Food and Drug Administration. (2019). Beyaz (drospirenone, ethinyl estradiol, and levomefolate calcium) prescribing information.
2. U.S. Food and Drug Administration. (2010). Safyral (drospirenone, ethinyl estradiol, and levomefolate calcium) approval and prescribing information.
3. U.S. Food and Drug Administration. (2012). Combined hormonal contraceptives containing drospirenone: Drug safety communication.
4. Bayer AG. (2023). Annual report 2023.
5. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book.
6. U.S. Food and Drug Administration. (2024). Abbreviated new drug application process.
7. U.S. Food and Drug Administration. (2023). Lupin Pharmaceuticals recalls Tydemy oral contraceptive tablets due to reduced assay.