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. |
| Molecular Weight | Levothyroxine (not applicable); TWIRLA contains levonorgestrel (312.45 Da) and ethinyl estradiol (296.40 Da). |
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 | Contraindicated due to risk of congenital defects; use of levonorgestrel and ethinyl estradiol is not recommended during pregnancy. |
| 2nd trimester | Contraindicated; no indication for use during pregnancy. |
| 3rd trimester | Contraindicated; may cause adverse effects such as jaundice and hepatotoxicity in the fetus. |
Clinical note
Comprehensive clinical and safety monograph for TWIRLA (TWIRLA).
| Placental transfer | Both components cross the placenta; ethinyl estradiol and levonorgestrel are known to transfer to fetal circulation. |
| Breastfeeding | Levonorgestrel and ethinyl estradiol are excreted in breast milk in small amounts; may reduce milk production and alter milk composition. Use only if benefits outweigh risks; consider alternative contraception. |
■ 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 |
Pregnancy or suspected pregnancyBreast cancerThromboembolic disordersHeavy smoking (>15 cigarettes/day) if age ≥35Hypertension with vascular diseaseDiabetes with vascular involvementMigraine with aura if age ≥35Severe liver disease
| 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 |
| Food/Dietary | No significant food interactions known. Grapefruit juice may slightly alter hormone metabolism but no specific restriction is required. Maintain consistent intake of folate-rich foods as the patch contains levomefolate; avoid large doses of folic acid supplements unless prescribed. |
Loading safety data…
| Lactation Rating |
| L4 |
| 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. |
| 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. |
| Clinical Pearls | TWIRLA is a combined hormonal contraceptive patch applied weekly for 3 weeks followed by a patch-free week. Ensure patch adhesion; if detached for more than 24 hours, apply a new patch and use backup contraception. Obesity (BMI ≥30) may reduce efficacy. Contraindicated in smokers over 35 due to increased thromboembolic risk. May reduce milk production if used during breastfeeding. |
| Patient Advice | Apply the patch once weekly on the same day for 3 consecutive weeks, then have a patch-free week. · Choose a clean, dry, hairless area on the buttock, abdomen, upper arm, or torso (not breasts). · Do not cut or alter the patch; if it fails to stick, apply a new one and keep the original schedule. · Use backup non-hormonal contraception (e.g., condoms) if patch is detached >24 hours or if starting late. · Do not smoke while using TWIRLA, especially if over 35 years old, due to increased risk of blood clots. · Notify your healthcare provider if you experience leg pain, chest pain, sudden shortness of breath, or severe headache. · TWIRLA does not protect against sexually transmitted infections (STIs); use condoms for STI prevention. · Store patches at room temperature away from direct sunlight and moisture. |