TRI-ESTARYLLA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TRI-ESTARYLLA (TRI-ESTARYLLA).
Combination hormonal contraceptive containing ethinyl estradiol and drospirenone. Ethinyl estradiol suppresses gonadotropin release, inhibiting ovulation. Drospirenone is a spironolactone analogue with anti-mineralocorticoid and antiandrogenic activity, also suppressing ovulation and increasing cervical mucus viscosity.
| Metabolism | Primarily via CYP3A4; ethinyl estradiol also undergoes sulfation. Drospirenone is metabolized via CYP3A4 and to a minor extent via reduction and subsequent glucuronidation. |
| Excretion | Renal: approximately 60% as unchanged drug and metabolites; Biliary/fecal: approximately 40%, primarily as metabolites. |
| Half-life | Terminal elimination half-life is 4-6 hours; clinical context: allows twice-daily dosing for stable blood levels. |
| Protein binding | Approximately 70-80% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Approximately 0.5-0.7 L/kg; clinical meaning: moderate distribution into total body water, with limited tissue penetration. |
| Bioavailability | Oral: approximately 90% due to minimal first-pass metabolism. |
| Onset of Action | Oral: 1-2 hours for initial therapeutic effect; peak effect at 3-5 hours. |
| Duration of Action | Oral: 8-12 hours; clinical note: sustained effect due to active metabolites, supporting twice-daily dosing. |
One tablet (ethinyl estradiol 0.03 mg / norgestimate 0.18-0.215-0.25 mg) orally once daily for 21 days followed by 7 placebo days.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required in mild-to-moderate renal impairment; contraindicated in severe renal disease due to potential fluid retention and hyperkalemia. |
| Liver impairment | Contraindicated in Child-Pugh class C (severe hepatic impairment); use with caution in Child-Pugh class A or B, with monitoring for signs of hepatotoxicity. |
| Pediatric use | Post-menarche only: same as adult dosing (one tablet daily); not indicated for pre-menarche use. |
| Geriatric use | Not indicated for postmenopausal use; higher risk of thromboembolism and cardiovascular events in women over 35 who smoke; consider non-hormonal contraceptives. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for TRI-ESTARYLLA (TRI-ESTARYLLA).
| Breastfeeding | Not recommended during breastfeeding. Small amount of ethinyl estradiol and levonorgestrel/ethinyl estradiol pass into milk. M/P ratio not well established. May reduce milk production and quality. |
| Teratogenic Risk | First trimester: Use not recommended due to risk of cardiovascular and neural tube defects. Second and third trimesters: Fetal exposure to estrogens and progestins may cause genitourinary tract abnormalities, but risk is low. Overall: Pregnancy contraindicated. |
| Fetal Monitoring |
■ FDA Black Box Warning
Cigarette smoking increases risk of serious cardiovascular events from combination oral contraceptives. Risk increases with age and heavy smoking (≥15 cigarettes/day). Women over 35 who smoke should not use this product.
| Serious Effects |
["Hypersensitivity to any component","Thrombophlebitis or thromboembolic disorders","Cerebrovascular or coronary artery disease","Known or suspected breast cancer or other estrogen-dependent neoplasia","Undiagnosed abnormal genital bleeding","Known or suspected pregnancy","Benign or malignant liver tumor or active liver disease","Uncontrolled hypertension","Diabetes with vascular involvement","Migraine with aura (age ≥35)","Renal impairment (GFR <30 mL/min/1.73 m² or history of kidney disease)","Adrenal insufficiency","Cigarette smoking in women over 35","Use of hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir with or without dasabuvir"]
| Precautions | ["Thrombotic disorders (including venous thromboembolism and arterial thromboembolism)","Liver disease (including hepatic adenoma, liver tumors)","Hypertension","Gallbladder disease","Carbohydrate and lipid metabolism effects","Headache/migraine","Menstrual irregularities and amenorrhea","Depression","Cervical cancer","Hereditary angioedema","Chloasma","Hepatitis C treatment interaction with ombitasvir/paritaprevir/ritonavir and dasabuvir"] |
Loading safety data…
| Monitor blood pressure, weight, and signs of thromboembolism. Inadvertent use during pregnancy: fetal ultrasound for anomalies. |
| Fertility Effects | Suppresses ovulation as contraceptive effect. After discontinuation, fertility returns to baseline. No permanent impairment. |