BEYAZ
Clinical safety rating
cautionComprehensive clinical and safety monograph for BEYAZ (BEYAZ).
Combination of ethinyl estradiol and drospirenone suppresses gonadotropins (FSH and LH) from the pituitary, inhibiting ovulation, altering cervical mucus, and inducing endometrial changes. Drospirenone is a spironolactone analogue with antimineralocorticoid and antiandrogenic activity.
| Metabolism | Primarily hepatic via CYP3A4. Ethinyl estradiol undergoes first-pass metabolism in the liver and gut wall. Drospirenone is metabolized via CYP3A4 and also undergoes reduction and sulfation. Metabolites are excreted in urine and feces. |
| Excretion | Urine (45-55% as metabolites), feces (30-40% as metabolites), with enterohepatic recirculation of ethinyl estradiol metabolites. |
| Half-life | Drospirenone: approximately 30 hours (terminal). Ethinyl estradiol: approximately 13-15 hours (terminal). Steady-state reached within 10 days. Clinical context: once-daily dosing maintains therapeutic levels with minimal accumulation after 3-4 cycles. |
| Protein binding | Drospirenone: 95-97% bound (primarily to albumin). Ethinyl estradiol: approximately 98% bound (mostly to albumin). |
| Volume of Distribution | Drospirenone: approximately 3.7 L/kg (suggests moderate tissue distribution). Ethinyl estradiol: approximately 3.6 L/kg (consistent with distribution into body water). Clinical meaning: not extensively stored in tissues. |
| Bioavailability | Oral: Drospirenone ~76% (relative to IV). Ethinyl estradiol ~55% (due to first-pass metabolism). |
| Onset of Action | Oral: Peak plasma concentrations at 1-3 hours for both components. Contraceptive effect begins after 7 consecutive days of dosing if started on day 1 of menstrual cycle; otherwise after 7 days of consistent use. |
| Duration of Action | 24 hours (once-daily dosing). The suppression of ovulation persists with regular daily intake. Missed-dose window: if <12 hours late, protection maintained; if >12 hours, backup contraception needed for 7 days. |
| Molecular Weight | 1008 |
| Action Class | Oral Contraceptive; Progestin and Estrogen Combination |
One tablet (drospirenone 3 mg / ethinyl estradiol 0.02 mg) orally once daily for 24 days, followed by 4 days of placebo.
| Dosage form | TABLET |
| Renal impairment | Contraindicated in patients with renal impairment (creatinine clearance < 50 mL/min). No dose adjustment is recommended for mild impairment (CrCl >= 50 mL/min); however, careful monitoring is advised. |
| Liver impairment | Contraindicated in patients with hepatic impairment (Child-Pugh class A, B, or C). Do not use in acute or chronic liver disease. |
| Pediatric use | Not indicated for use before menarche. For postmenarchal adolescents, dose is same as adults: one tablet daily following the 24/4 regimen. |
| Geriatric use | Not indicated for use in postmenopausal women. No specific geriatric dosing is established; use not recommended in this population. |
| 1st trimester | Contains drospirenone and ethinyl estradiol; malformation risk not significantly increased in large studies. |
| 2nd trimester | Risk of fetal harm; avoid use due to potential adverse effects on pregnancy and fetal development. |
| 3rd trimester | Contraindicated during pregnancy; may cause harm to fetus including possible estrogenic effects. |
Clinical note
Comprehensive clinical and safety monograph for BEYAZ (BEYAZ).
| Placental transfer | Yes, ethinyl estradiol and drospirenone cross the placenta; documented in animal and human studies. |
| Breastfeeding | Small amounts pass into breast milk; may reduce milk production and composition; use only if clearly needed. |
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | Pregnancy category X. Contraindicated in pregnancy due to known teratogenic effects, including cardiovascular and skeletal anomalies, particularly during first trimester. Use during second and third trimesters is associated with feminization of male fetuses and potential hepatic adenoma. Discontinue immediately if pregnancy occurs. |
| Fetal Monitoring | Pregnancy test prior to initiation and monthly thereafter. Monitor for signs of thromboembolism, hypertension, glucose intolerance, and hepatic dysfunction. Fetal ultrasound for anomalies if inadvertent exposure occurs. |
| Fertility Effects | Suppresses ovulation via inhibition of gonadotropins. After discontinuation, return to fertility may be delayed (up to several months). No permanent negative impact on fertility; may be used in cycle regulation for infertility treatment. |
■ FDA Black Box Warning
Cigarette smoking increases the risk of serious cardiovascular events from combination oral contraceptives (COCs). This risk increases with age, especially in women over 35 years, and with the number of cigarettes smoked. Women who use COCs should be strongly advised not to smoke.
| Common Effects | Nausea, Headache, Breast tenderness, Irregular uterine bleeding, Weight changes, Mood changes |
| Serious Effects | Venous thromboembolism (VTE), Arterial thromboembolism (e.g., stroke, myocardial infarction), Hypertension, Hepatic adenoma or hepatocellular carcinoma, Gallbladder disease, Hyperkalemia (due to drospirenone's antimineralocorticoid activity) |
PregnancyBreast cancerCurrent or history of venous thromboembolismCerebrovascular diseaseCoronary artery diseaseHepatic adenoma or liver tumorUncontrolled hypertension
| Precautions | Thrombotic disorders: venous thromboembolism, arterial thromboembolism, stroke, myocardial infarction, Hepatic disease: jaundice, cholestasis, hepatic adenomas, Hypertension: monitor blood pressure, Hyperkalemia: risk in patients with renal impairment, hepatic impairment, or adrenal insufficiency; avoid use with potassium-sparing diuretics or potassium supplements, Gallbladder disease, Carbohydrate and lipid metabolic effects, Headache/migraine, Bleeding irregularities, Depression, Carcinoma: breast and cervical, Ocular lesions: retinal thrombosis |
| Food/Dietary | Grapefruit and grapefruit juice should be avoided as they inhibit CYP3A4, potentially increasing ethinyl estradiol levels and risk of adverse effects. No other specific food interactions are documented, but consider that high potassium foods (e.g., bananas, oranges, spinach) may theoretically contribute to hyperkalemia in susceptible patients, though routine avoidance is not required. Alcohol may increase the risk of liver toxicity, but moderate use is not contraindicated. |
| Clinical Pearls | BEYAZ (drospirenone/ethinyl estradiol) is a combined oral contraceptive (COC) with a 24/4 regimen. The drospirenone component has antimineralocorticoid activity, which can be beneficial for patients with fluid retention or acne. Monitor potassium levels in patients on concomitant medications that increase potassium (e.g., ACE inhibitors, ARBs, NSAIDs). BEYAZ is contraindicated in patients with renal impairment (CrCl <30 mL/min) due to risk of hyperkalemia. The 24 active pill regimen provides a longer window of ovulation suppression and may reduce breakthrough bleeding compared to 21-day regimens. Use with caution in patients with a history of depression; drospirenone may affect mood. |
| Patient Advice | Take one pill at the same time each day, preferably in the evening to minimize nausea. · If you miss a pill, follow the package insert instructions: for one missed pill, take it as soon as remembered; for two or more missed pills, use backup contraception (e.g., condoms) for at least 7 days. · Avoid eating grapefruit or drinking grapefruit juice while taking this medication because it can increase estrogen levels and risk of side effects. · Do not smoke while using BEYAZ, especially if you are over 35, as smoking increases the risk of serious cardiovascular events. · Side effects may include nausea, breast tenderness, headache, and mood changes; report persistent symptoms to your provider. · Seek immediate medical attention if you experience signs of a blood clot: sudden leg swelling, chest pain, shortness of breath, or sudden severe headache. · BEYAZ does not protect against HIV or other sexually transmitted infections; use condoms for protection. |
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