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. |
| Molecular Weight | Ethinyl estradiol: 296.4 Da; Norgestimate: 369.5 Da (pro-drug for levonorgestrel: 312.5 Da). Combined formulation weight varies by component; typical molecular weight of active metabolites is ~300-370 Da. |
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 | Pregnancy category X. Contraindicated due to risk of fetal harm, including cardiovascular and limb defects from estrogen component, and virilization of female fetus from progestin. Use alternative contraception. If exposure occurs, evaluate pregnancy. |
| 2nd trimester | Same as first trimester: contraindicated. Estrogen and progestin are known teratogens. Avoid use. |
| 3rd trimester | Contraindicated in third trimester due to risk of uterine bleeding, premature labor, and fetal harm. Discontinue if pregnancy is suspected. |
Clinical note
Comprehensive clinical and safety monograph for TRI-LO-ESTARYLLA (TRI-LO-ESTARYLLA).
| Placental transfer | Both ethinyl estradiol and norgestimate/levonorgestrel cross the placenta. Ethinyl estradiol is detected in fetal cord blood at maternal serum levels. Progestins achieve fetal concentrations approximately 50% of maternal levels. Transfer is rapid due to lipophilicity. |
| Breastfeeding |
■ 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 |
Known or suspected pregnancyCurrent or history of thromboembolic disorders (e.g., DVT, PE)Cerebrovascular or coronary artery diseaseActive liver disease or impaired liver function (e.g., hepatitis, cirrhosis)Undiagnosed abnormal uterine bleedingKnown or suspected breast cancer or estrogen-dependent neoplasiaMigraine with aura (age >35)Smoking >15 cigarettes/day in women >35 yearsUncontrolled hypertension (>160/100 mmHg)Diabetes with vascular involvementMajor surgery with prolonged immobilization
| 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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| Small amounts of ethinyl estradiol and norgestimate/levonorgestrel are excreted into breast milk. Use in breastfeeding is generally not recommended due to potential adverse effects on infant hormone levels and milk production. The American Academy of Pediatrics considers combined hormonal contraceptives as 'maternal medication usually compatible with breastfeeding' after postpartum period, but alternative methods (e.g., progestin-only) are preferred. Discuss risks and benefits with patient. |
| Lactation Rating | L4 (Possibly Hazardous) - based on risk of decreasing milk supply and infant exposure to ethinyl estradiol. |
| 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. |
| 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. |
| Food/Dietary | No specific food restrictions. Grapefruit juice may slightly increase estrogen levels but is not considered clinically significant. High-fat meals may delay absorption slightly but do not reduce efficacy. |
| Clinical Pearls | Tri-Lo-Estarylla is a triphasic oral contraceptive containing ethinyl estradiol and norgestimate. It is important to counsel patients about the increased risk of venous thromboembolism, especially in smokers over 35. The low estrogen dose (25 mcg) may be associated with breakthrough bleeding, which typically improves after 3-6 months. Efficacy relies on consistent daily intake; missing doses requires backup contraception per package instructions. Drug interactions with rifampin, certain anticonvulsants, and St. John's wort can reduce efficacy. |
| Patient Advice | Take one pill daily at the same time, following the order on the pack. Missed pills increase pregnancy risk; refer to package insert for missed dose instructions. · Do not smoke while taking this medication, especially if over 35, due to increased risk of blood clots, stroke, or heart attack. · Common side effects include nausea, headache, breast tenderness, and spotting. These often improve after a few months. · Use backup contraception (e.g., condoms) if you miss pills, vomit within 4 hours of taking a pill, or start a new medication that may interact. · Contact your healthcare provider immediately if you experience signs of a blood clot: leg pain/swelling, sudden shortness of breath, chest pain, or severe headache. · This medication does not protect against HIV or other sexually transmitted infections. |