TRI-LO-ESTARYLLA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TRI-LO-ESTARYLLA (TRI-LO-ESTARYLLA).
Combination oral contraceptive containing ethinyl estradiol and norgestimate. Suppresses gonadotropin secretion, primarily FSH and LH, inhibiting ovulation; increases cervical mucus viscosity, impeding sperm penetration; alters endometrial lining, reducing implantation likelihood.
| Metabolism | Ethinyl estradiol: metabolized primarily via CYP3A4, undergoes first-pass metabolism, conjugation to glucuronides and sulfates. Norgestimate: rapidly deacetylated to norgestrel (active metabolite), further hydroxylated and conjugated; metabolism involves CYP3A4 and other CYP enzymes. |
| Excretion | Renal: ~40% as metabolites; Fecal: ~30% as metabolites (including ethinyl estradiol conjugates); Biliary: ~20% (enterohepatic recirculation). |
| Half-life | Ethinyl estradiol: 19-24 hours (terminal); Norgestimate: active metabolite norelgestromin 28-38 hours; allows once-daily dosing. |
| Protein binding | Ethinyl estradiol: ~97-98% bound to albumin; Norgestimate/norelgestromin: ~99% bound to SHBG and albumin. |
| Volume of Distribution | Ethinyl estradiol: 1.5-3 L/kg; Norelgestromin: 2-4 L/kg; reflects extensive tissue distribution. |
| Bioavailability | Oral: Ethinyl estradiol ~45% (first-pass metabolism); Norgestimate extensively metabolized to active norelgestromin (bioavailability not directly applicable). |
| Onset of Action | Oral: 7 days of consecutive dosing required for full contraceptive effect (suppression of ovulation); immediate if started on day 1 of menses. |
| Duration of Action | 24 hours (maintains steady hormone levels for once-daily dosing); contraceptive efficacy requires consistent daily administration. |
One tablet (20 mcg ethinyl estradiol/0.1 mg levonorgestrel) orally once daily for 21 days, followed by 7 days of placebo.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment. Contraindicated in severe renal impairment or acute renal failure. |
| Liver impairment | Contraindicated in patients with acute or chronic hepatic dysfunction, including Child-Pugh class A, B, or C, until liver function returns to normal. |
| Pediatric use | Not indicated for use in females before menarche. For postmenarcheal adolescents, same dosing as adults (one tablet daily for 21 days, then 7 days placebo). |
| Geriatric use | Not indicated for use in females after menopause. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for TRI-LO-ESTARYLLA (TRI-LO-ESTARYLLA).
| Breastfeeding | Contraindicated during lactation. Estrogens and progestins are excreted in breast milk in small amounts (M/P ratio unknown for triphasic regimen). May reduce milk production and infant exposure to steroids. Alternative contraception recommended. |
| Teratogenic Risk | FDA Pregnancy Category X. Contraindicated in pregnancy due to known teratogenic effects. First trimester: increased risk of cardiovascular defects, neural tube defects, and oral clefts. Second and third trimesters: potential for fetal harm including masculinization of female fetuses from progestins. Discontinue immediately if pregnancy occurs. |
■ FDA Black Box Warning
Cigarette smoking increases risk of serious cardiovascular events (e.g., thromboembolism, stroke, myocardial infarction) from combination oral contraceptive use, especially in women >35 years who smoke. Concomitant smoking is contraindicated in women >35 years.
| Serious Effects |
["Current or past venous thromboembolism (e.g., deep vein thrombosis, pulmonary embolism)","Cerebrovascular or coronary artery disease (e.g., stroke, myocardial infarction)","Thrombogenic valvular or rhythm disorders (e.g., atrial fibrillation with thrombogenic risk)","Uncontrolled hypertension (sustained blood pressure ≥160/≥100 mmHg)","Diabetes with vascular involvement","Headaches with focal neurological symptoms or migraine with aura (any age) or migraine without aura if >35 years","Biliary tract disease (including cholestatic jaundice of pregnancy or prior pill use)","Liver tumors (benign or malignant), acute hepatitis, or severe cirrhosis","Known or suspected pregnancy","Hypersensitivity to any component","Carcinoma of the breast or endometrium or other estrogen-sensitive neoplasia","Undiagnosed abnormal uterine bleeding","Cigarette smoking in women >35 years","Use of Hepatitis C combination regimen containing ombitasvir/paritaprevir/ritonavir with or without dasabuvir"]
| Precautions | ["Thromboembolic disorders and cardiovascular risks including venous thromboembolism, arterial thromboembolism, stroke, myocardial infarction","Hepatic neoplasia: benign and malignant liver tumors reported","Gallbladder disease","Elevated blood pressure","Carbohydrate and lipid metabolism effects","Headache/migraine exacerbation","Bleeding irregularities including amenorrhea and breakthrough bleeding","Depression","Hereditary angioedema","Chloasma","Folate levels reduction","Potential for reduced contraceptive efficacy with hepatic enzyme inducers","Reduced efficacy and increased breakthrough bleeding with CYP3A4 inducers"] |
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| Fetal Monitoring | Not applicable as drug is contraindicated in pregnancy. For accidental exposure, monitor fetal development via ultrasound, echocardiography if exposure in first trimester. Assess for signs of masculinization in female fetuses. Conduct pregnancy test prior to initiation and monthly thereafter. |
| Fertility Effects | Delays return to fertility after discontinuation; median time to conception is 3-6 months after stopping combined hormonal contraceptives. No permanent negative impact on fertility. |