What are the usage guidelines and potential risks for Beyaz (drospirenone, ethinyl estradiol, and levomefolate), a combination oral contraceptive?

Beyaz: Usage Guidelines and Potential Risks

Beyaz (drospirenone 3 mg, ethinyl estradiol 0.02 mg, and levomefolate calcium 0.451 mg) is FDA-approved for contraception, treatment of moderate acne in women at least 14 years of age, treatment of premenstrual dysphoric disorder (PMDD), and folate supplementation to reduce the risk of neural tube defects in a pregnancy conceived while taking the product or shortly after discontinuation. 1

Indications and Benefits

• Beyaz is a combined oral contraceptive (COC) that contains 24 pink active tablets with hormones followed by 4 light orange tablets with only levomefolate calcium 1
• Primary indication is pregnancy prevention with typical failure rates of 7-9% with typical use 2
• Additional approved indications include:
  • Treatment of moderate acne vulgaris in women ≥14 years who have achieved menarche 1
  • Treatment of PMDD symptoms in women choosing oral contraception 1
  • Folate supplementation to reduce neural tube defect risk in pregnancies conceived during use or shortly after discontinuation 1, 3

Mechanism of Action

• Prevents pregnancy by inhibiting gonadotropin-releasing hormone, follicle-stimulating hormone, and luteinizing hormone, preventing ovulation 4
• Drospirenone is a fourth-generation progestin with antimineralocorticoid and antiandrogenic properties 5
• Levomefolate calcium component increases red blood cell and plasma folate levels to values protective against neural tube defects 3
• After discontinuation, elevated red blood cell folate levels remain in 85% of women at 4 weeks and 60% at 8 weeks 3

Administration Guidelines

• Take one tablet daily at the same time every day in the order directed on the blister pack 1
• If one hormonal pill is late (<24 hours):
  • Take the late pill as soon as possible
  • Continue taking remaining pills at the usual time
  • No additional contraceptive protection needed 4
• If one hormonal pill is missed (24 to <48 hours):
  • Take the most recent missed pill as soon as possible
  • Continue taking remaining pills at the usual time
  • Use backup contraception until hormonal pills have been taken for 7 consecutive days 4
• If two or more consecutive hormonal pills are missed (≥48 hours):
  • Take the most recent missed pill immediately
  • Continue taking remaining pills at the usual time
  • Use backup contraception until hormonal pills have been taken for 7 consecutive days
  • Consider emergency contraception if pills were missed during the first week and unprotected intercourse occurred in the previous 5 days 4

Contraindications

Beyaz is contraindicated in women with:

• Cigarette smoking if age ≥35 years 1
• Renal impairment or adrenal insufficiency 1
• High risk of arterial or venous thrombotic diseases 1
• Undiagnosed abnormal uterine bleeding 1
• Breast cancer or other estrogen/progestin-sensitive cancer 1
• Liver tumors or liver disease 1
• Pregnancy 1
• Co-administration with Hepatitis C drug combinations containing ombitasvir, paritaprevir/ritonavir, with or without dasabuvir 1

Potential Risks and Side Effects

Common Side Effects

• Headache/migraine (5.9%) 1
• Menstrual irregularities (4.1%) 1
• Nausea/vomiting (3.5%) 1
• Breast pain/tenderness (3.2%) 1
• For PMDD indication: higher rates of menstrual irregularities (24.9%), nausea (15.8%), headache (13.0%), and breast tenderness (10.5%) 1

Serious Risks

• Venous thromboembolism (VTE): COCs containing drospirenone may be associated with a higher risk of VTE than COCs containing levonorgestrel or some other progestins 1
• Hyperkalemia: Due to drospirenone's anti-mineralocorticoid activity, monitor serum potassium during the first treatment cycle in women on medications that may increase potassium 1
• Cardiovascular risks: Stop Beyaz if a thrombotic event occurs 1
• Liver disease: Discontinue if jaundice develops 1
• Hypertension: Do not prescribe for women with uncontrolled hypertension or hypertension with vascular disease 1

Special Considerations

Drug Interactions

• Rifampin and griseofulvin can reduce COC effectiveness 4
• Most antibiotics, including tetracyclines, do not reduce COC effectiveness 4
• Concomitant use of spironolactone with drospirenone-containing COCs has not shown significant elevations in serum potassium or additional side effects requiring treatment discontinuation 4

Monitoring Requirements

• Blood pressure should be assessed before initiation 2
• Check serum potassium during the first treatment cycle in women on long-term medications that may increase serum potassium 1
• Evaluate any significant changes in headaches or irregular bleeding patterns 1

Clinical Pearls

• Acne improvement may not be appreciated until after the first few months of treatment 4
• A Papanicolaou smear and bimanual pelvic examination are not mandatory before initiating Beyaz 4
• Women who frequently miss COCs should consider an alternative contraceptive method that is less dependent on user compliance (e.g., IUD, implant, or injectable) 4
• Beyaz provides folate supplementation that may help reduce neural tube defect risk in pregnancies conceived during use or shortly after discontinuation 3