TWIRLA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TWIRLA (TWIRLA).
Combination hormonal contraceptive that inhibits gonadotropin secretion (FSH and LH) through estrogen and progestin, suppressing ovulation; increases cervical mucus viscosity and alters endometrial receptivity.
| Metabolism | Ethinyl estradiol: CYP3A4, glucuronidation; Levonorgestrel: CYP3A4, reduction, sulfation, glucuronidation. |
| Excretion | Primarily renal (about 60% as metabolites, <10% unchanged) and fecal (about 30-40% as metabolites). |
| Half-life | Levonorgestrel: approximately 25 hours (range 17-30 h). Ethinyl estradiol: approximately 13 hours (range 10-16 h). Clinical context: Steady state reached within 5-7 days; half-life supports once-weekly dosing. |
| Protein binding | Levonorgestrel: 97-99% bound to sex hormone-binding globulin (SHBG) and albumin. Ethinyl estradiol: 98% bound to albumin, induces SHBG synthesis. |
| Volume of Distribution | Levonorgestrel: approximately 1.8 L/kg. Ethinyl estradiol: approximately 2.5 L/kg. Indicates extensive tissue distribution (e.g., adipose, reproductive organs). |
| Bioavailability | Transdermal patch: approximately 100% (no first-pass metabolism, avoids hepatic extraction). Oral (reference): levonorgestrel 89-100%, ethinyl estradiol 45% (due to first-pass). |
| Onset of Action | Transdermal: Contraceptive effect begins after 7 days of continuous use (first week requires backup contraception). |
| Duration of Action | Each patch provides contraceptive coverage for 7 days. Replace weekly for 3 weeks, then patch-free week. Clinical notes: Consistent serum levels maintained during wear; delayed patch application reduces efficacy. |
One patch applied to the lower abdomen, buttocks, or upper torso once weekly for 3 consecutive weeks (21 days) followed by a 7-day patch-free interval. Each patch releases 120 mcg of levonorgestrel and 30 mcg of ethinyl estradiol per 24 hours.
| Dosage form | SYSTEM |
| Renal impairment | No adjustment required for mild to moderate impairment. Contraindicated in severe renal impairment (CrCl < 30 mL/min) due to potential hormonal and metabolic effects. |
| Liver impairment | Contraindicated in acute or chronic hepatic dysfunction, including Child-Pugh Class B and C, due to impaired steroid metabolism. |
| Pediatric use | Approved for postmenarchal adolescents. Same dosing as adults. Not indicated before menarche. |
| Geriatric use | Not indicated for use in postmenopausal women. Contraindicated in women over 35 years of age who smoke ≥15 cigarettes per day. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for TWIRLA (TWIRLA).
| Breastfeeding | TWIRLA may reduce milk production, especially in early breastfeeding. Estrogen component can decrease quantity and quality. Use only if benefits outweigh risks; recommend non-hormonal methods. M/P ratio: Not provided by manufacturer; levonorgestrel M/P ~0.7, ethinyl estradiol ~0.04 (limited data). Monitor infant for jaundice, growth. Avoid in first 21 days postpartum due to thromboembolic risk. |
| Teratogenic Risk | TWIRLA (levonorgestrel/ethinyl estradiol) is a combined hormonal contraceptive. Use during pregnancy is contraindicated. First trimester: Major malformation risk not increased above baseline (2-3%) in cohort studies, but no indication for use. Second/Third trimester: Fetal exposure to estrogens/progestins may cause masculinization of female genitalia (clitoral hypertrophy, labial fusion) and virilization. Postpartum: Transient withdrawal bleeding possible. Overall: Not for use in pregnancy. |
■ FDA Black Box Warning
Cigarette smoking increases risk of serious cardiovascular events with combination hormonal contraceptive use. Risk increases with age and smoking amount (especially >35 years and ≥15 cigarettes/day).
| Serious Effects |
["Current or history of thrombotic disorders or thromboembolic disease","Cerebrovascular or coronary artery disease","Known or suspected pregnancy","Current or history of breast cancer (or other estrogen- or progestin-sensitive cancer)","Liver tumors (benign or malignant) or active liver disease","Undiagnosed abnormal uterine bleeding","Use of Hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir with or without dasabuvir","Hypersensitivity to any component"]
| Precautions | ["Thrombotic disorders including venous thromboembolism and arterial thrombosis","Myocardial infarction and stroke","Cerebrovascular disease","Liver disease (e.g., hepatic adenoma, jaundice)","Hypertension","Carbohydrate and lipid metabolism effects","Headache/migraine","Bleeding irregularities","Ectopic pregnancy risk","Gallbladder disease","Depression","Hereditary angioedema","Chloasma","Ocular changes including contact lens intolerance"] |
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| Fetal Monitoring | If inadvertent exposure during pregnancy, no specific monitoring required beyond routine prenatal care. For lactating women: monitor infant weight gain, development. Monitor maternal blood pressure, signs of thromboembolism. Not recommended during pregnancy; if used, assess fetal growth and development via ultrasound. |
| Fertility Effects | TWIRLA suppresses ovulation via hypothalamic-pituitary-ovarian axis inhibition. Reversible: return of ovulatory cycles typically occurs within 1-3 months after discontinuation. No permanent effect on fertility reported. May cause amenorrhea during use; post-discontinuation, fertility returns to baseline. |