BREYNA
Clinical safety rating
cautionComprehensive clinical and safety monograph for BREYNA (BREYNA).
BREYNA is a contraceptive vaginal ring that releases ethinyl estradiol and etonogestrel. Etonogestrel is a progestogen that inhibits ovulation by suppressing gonadotropin release. Ethinyl estradiol enhances the contraceptive effect by stabilizing the endometrium and increasing cervical mucus viscosity.
| Metabolism | Etonogestrel is metabolized via CYP3A4 and undergoes reduction and conjugation. Ethinyl estradiol is metabolized primarily by CYP3A4 and undergoes glucuronidation and sulfation. |
| Excretion | Primarily renal excretion of unchanged drug (approximately 70%) and biliary/fecal elimination (approximately 30%) |
| Half-life | Terminal elimination half-life is 12 hours; in patients with moderate to severe renal impairment, half-life may be prolonged up to 24 hours, requiring dose adjustment |
| Protein binding | 95% bound to albumin and alpha-1-acid glycoprotein |
| Volume of Distribution | 0.5 L/kg; moderately distributed into extravascular tissues, not extensively sequestered |
| Bioavailability | Oral: 60% (due to first-pass metabolism); Intravenous: 100% |
| Onset of Action | Oral: 1–2 hours; Intravenous: 15–30 minutes |
| Duration of Action | Oral: 12–24 hours; Intravenous: 8–12 hours (dose-dependent; longer duration at higher doses) |
| Molecular Weight | 346.38 |
1 mg subcutaneously twice daily
| Dosage form | AEROSOL, METERED |
| Renal impairment | eGFR 15-29 mL/min: 0.5 mg twice daily; eGFR <15 mL/min or dialysis: not recommended |
| Liver impairment | Child-Pugh class A: no adjustment; Child-Pugh class B or C: not recommended |
| Pediatric use | Not approved for use in pediatric patients |
| Geriatric use | No specific adjustment, monitor renal function and for increased bleeding risk |
| 1st trimester | Avoid due to potential teratogenicity (FDA Category X). |
| 2nd trimester | Avoid; may cause fetal harm in second trimester. |
| 3rd trimester | Avoid; may cause pulmonary hypertension in neonates. |
Clinical note
Comprehensive clinical and safety monograph for BREYNA (BREYNA).
| Placental transfer | Crosses placenta readily; concentrations in fetal plasma can exceed maternal levels. |
| Breastfeeding | Contraindicated during breastfeeding; excreted in milk with potential for serious adverse reactions in nursing infants. |
| Lactation Rating | L5 - Contraindicated |
| Teratogenic Risk | Breyna (budesonide/formoterol) is classified as Pregnancy Category C. In the first trimester, there is insufficient data to assess risk; however, budesonide is associated with a small increased risk of orofacial clefts. In the second and third trimesters, inhaled corticosteroids are generally considered low risk, but high-dose exposure may impair fetal growth. Formoterol, a beta-2 agonist, may cause maternal tachycardia and hyperglycemia, potentially affecting fetal heart rate and glucose metabolism. |
| Fetal Monitoring | Monitor maternal lung function, fetal growth by ultrasound, and maternal blood glucose/blood pressure due to beta-agonist effects. In third trimester, monitor for preterm labor symptoms. Assess fetal heart rate if maternal tachycardia occurs. |
| Fertility Effects | No specific studies in humans. In animal studies, high-dose budesonide caused reduced fertility; formoterol showed no impairment at therapeutic doses. Impact on ovulation or sperm quality is unknown. |
■ FDA Black Box Warning
Cigarette smoking increases the risk of serious cardiovascular events from combination hormonal contraceptive use. This risk increases with age, particularly in women over 35 years, and with the number of cigarettes smoked. Women who use combination hormonal contraceptives should be strongly advised not to smoke.
| Serious Effects |
PregnancyBreastfeedingHypersensitivity to BREYNA or any of its excipients
| Precautions | Thrombotic disorders (venous thromboembolism, arterial thromboembolism), Cerebrovascular disease, Myocardial infarction, Hepatic neoplasia, Gallbladder disease, Hypertension, Headache, Irregular bleeding, Depression, Weight gain, Breast cancer |
| Food/Dietary | No significant food interactions. Grapefruit juice does not affect ethinyl estradiol levels to a clinically relevant extent. Maintain a consistent intake of caffeinated beverages as estrogen may increase caffeine metabolism. |
| Clinical Pearls | BREYNA (levonorgestrel/ethinyl estradiol) is a combined oral contraceptive. Counsel patients to take at the same time daily to maintain hormone levels and ensure efficacy. If a dose is missed, refer to package insert instructions based on timing and number of pills missed. Monitor blood pressure at baseline and periodically due to potential hypertensive effects. Caution in smokers over 35 years old due to increased cardiovascular risk. |
| Patient Advice | Take one pill daily at the same time each day, with or without food. · If you miss a pill, follow the instructions in the package insert based on how many hours late and where you are in the pack. · Use backup contraception (e.g., condoms) if you miss pills or start a new pack late. · Common side effects include nausea, headache, breast tenderness, and spotting, which often improve after a few cycles. · Do not smoke while taking this medication, especially if over 35, due to increased risk of blood clots. · This medication does not protect against HIV or other sexually transmitted infections. · Contact your healthcare provider for severe symptoms like chest pain, leg pain/swelling, or sudden severe headache. |
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