What are the indications and uses of Beyaz (drospirenone, ethinyl estradiol, and levomefolate)?

Indications and Uses of Beyaz (Drospirenone, Ethinyl Estradiol, and Levomefolate)

Beyaz is a combination oral contraceptive (COC) containing drospirenone, ethinyl estradiol, and levomefolate calcium that is FDA-approved for contraception, treatment of premenstrual dysphoric disorder (PMDD), treatment of moderate acne in women at least 14 years old, and folate supplementation to reduce the risk of neural tube defects in pregnancies conceived during use or shortly after discontinuation. 1, 2

Primary Indications

1. Contraception

• Beyaz contains 3 mg drospirenone and 20 μg ethinyl estradiol in a 24/4-day regimen (24 active tablets followed by 4 inactive tablets)
• Provides 99% contraceptive protection over 1 year of treatment 3
• Taken daily at the same time in the order directed on the blister pack 1

2. Premenstrual Dysphoric Disorder (PMDD)

• Indicated for treatment of PMDD symptoms in women who choose to use an oral contraceptive for contraception 1
• Clinical trials demonstrate significant improvement in both emotional and physical symptoms of PMDD 4
• Drospirenone-containing COCs showed greater mean decreases in:
  • Impairment of productivity
  • Social activities
  • Relationships 4

3. Moderate Acne

• Indicated for treatment of moderate acne in women at least 14 years old who desire contraception 1
• Effective in reducing inflammatory, non-inflammatory, and total acne lesions 5
• Drospirenone has anti-androgenic properties that help reduce sebum production 6

4. Folate Supplementation

• Contains 451 μg levomefolate calcium in all 28 tablets 2
• Significantly increases red blood cell and plasma folate levels 2
• Helps reduce the risk of neural tube defects in pregnancies conceived during use or shortly after discontinuation 2
• After discontinuation, protective folate levels (>906 nmol/l) remain in 85% of women at 4 weeks and 60% at 8 weeks 2

Mechanism of Action

Contraceptive Effects

• Inhibits ovulation
• Increases cervical mucus viscosity
• Alters endometrial receptivity

Anti-Androgenic Effects

• Drospirenone decreases ovarian androgen production
• Increases sex hormone-binding globulin (SHBG)
• Reduces 5α-reductase activity
• Blocks androgen receptors 6

Anti-Mineralocorticoid Effects

• Drospirenone has anti-mineralocorticoid properties similar to spironolactone 6, 7
• May help reduce fluid retention and associated symptoms

Important Safety Considerations

Cardiovascular Risks

• Women over 35 years old who smoke should not use Beyaz 1
• Increased risk of venous thromboembolism (VTE) compared to other COCs:
  • Drospirenone-containing COCs: ~10 per 10,000 woman-years
  • Other COCs: 3-9 per 10,000 woman-years
  • Non-users: 1-5 per 10,000 woman-years 5
• Increased risk of myocardial infarction and stroke, particularly in smokers and women with hypertension 5

Hyperkalemia Risk

• Drospirenone has anti-mineralocorticoid activity
• Not recommended for patients predisposed to hyperkalemia
• Serum potassium should be checked during the first treatment cycle in women on medications that may increase potassium levels 1

Contraindications

• Renal impairment
• Adrenal insufficiency
• High risk of arterial or venous thrombotic diseases
• Undiagnosed abnormal uterine bleeding
• Breast cancer
• Liver tumors or liver disease
• Co-administration with Hepatitis C drug combinations containing ombitasvir, paritaprevir/ritonavir, with or without dasabuvir 1

Common Side Effects

• Headache/migraine (6.7%)
• Menstrual irregularities (4.7%)
• Nausea/vomiting (4.2%)
• Breast pain/tenderness (4.0%)
• Mood changes (2.2%) 1
• Intermenstrual bleeding 4

Clinical Decision-Making Algorithm

1. For women seeking contraception who also have:

   • PMDD symptoms → Consider Beyaz as first-line option
   • Moderate acne → Consider Beyaz as first-line option
   • Need for folate supplementation → Beyaz provides added benefit

2. Avoid Beyaz in women with:

   • Age ≥35 years who smoke
   • History of VTE or high risk of thrombosis
   • Renal impairment or risk of hyperkalemia
   • Uncontrolled hypertension
   • Liver disease

3. Monitor:

   • Blood pressure at baseline and follow-up
   • Serum potassium in first cycle for women on medications that may increase potassium
   • Improvement in PMDD symptoms and acne after 3 months
   • Side effects and adherence

Practical Considerations

• The 24/4 regimen (24 active pills, 4 inactive) may provide better symptom control than traditional 21/7 regimens by reducing hormone fluctuations 7
• The folate component provides protection against neural tube defects that persists for several weeks after discontinuation 2
• Drug interactions with CYP3A4 inducers may decrease effectiveness; backup contraception should be used 1