NUVARING
Clinical safety rating: caution
Comprehensive clinical and safety monograph for NUVARING (NUVARING).
Combination hormonal contraceptive containing etonogestrel and ethinyl estradiol. Inhibits ovulation by suppressing gonadotropin release, increases cervical mucus viscosity to impede sperm penetration, and alters endometrial receptivity.
| Metabolism | Etonogestrel: CYP3A4 and CYP2C9. Ethinyl estradiol: CYP3A4, with glucuronidation and sulfation. |
| Excretion | Etonogestrel is excreted primarily in urine (38%) and feces (54%) as metabolites. The 3-keto-desogestrel metabolite is also excreted renally and fecally. Approximately 20% of the dose is excreted unchanged in urine for etonogestrel, but the majority is conjugated metabolites. |
| Half-life | The terminal elimination half-life for etonogestrel is approximately 29 hours (range 24-34 hours). This supports once-weekly dosing as the elimination half-life allows stable serum concentrations over the 3-week insertion period. |
| Protein binding | Etonogestrel is highly bound to serum proteins: 95-99%, primarily to albumin (30-40%) and sex hormone-binding globulin (SHBG, 60-70%). The binding to SHBG is saturable at higher concentrations. |
| Volume of Distribution | The apparent volume of distribution for etonogestrel is approximately 2.3 L/kg. This large Vd indicates extensive distribution into tissues, including adipose tissue, and accounts for the slow elimination. |
| Bioavailability | Bioavailability via vaginal route is approximately 100% for etonogestrel, as it is directly absorbed across the vaginal mucosa into systemic circulation, bypassing first-pass hepatic metabolism. |
| Onset of Action | Onset of contraceptive effect occurs within 7 days of insertion if the ring is inserted on the first day of menstruation. If inserted later, backup contraception is needed for 7 days. Ovulation suppression is achieved within 72 hours of initial insertion based on hormonal levels. |
| Duration of Action | Duration of action is 3 weeks (21 days) of continuous use. After removal, contraceptive effect declines but may persist for up to 7 days. The ring must be removed after 3 weeks to allow withdrawal bleeding and is replaced after a 1-week ring-free interval. |
One vaginal ring inserted and left in place for 3 weeks, followed by a 1-week ring-free period. Each ring releases 0.120 mg etonogestrel and 0.015 mg ethinyl estradiol per day.
| Dosage form | RING |
| Renal impairment | Contraindicated in severe renal impairment (CrCl < 30 mL/min). No dose adjustment required for mild to moderate impairment. |
| Liver impairment | Contraindicated in acute liver disease or decompensated cirrhosis (Child-Pugh class B or C). Not studied in mild hepatic impairment (Child-Pugh class A) but caution advised. |
| Pediatric use | Not approved for use in postmenarchal pediatric patients; no established safety and efficacy data. |
| Geriatric use | Not indicated for use in postmenopausal women. No geriatric-specific studies; consider increased risk of thromboembolism. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for NUVARING (NUVARING).
| Breastfeeding | Excreted in breast milk; M/P ratio not established. May reduce milk production and composition. Caution advised; alternative contraception recommended. |
| Teratogenic Risk | FDA Pregnancy Category X. First trimester: increased risk of cardiovascular defects and neural tube defects. Second and third trimesters: associated with fetal genital tract abnormalities and potential for other malformations. Use contraindicated in pregnancy. |
| Fetal Monitoring |
■ FDA Black Box Warning
Cigarette smoking increases risk of serious cardiovascular events from combination hormonal contraceptive use. Risk increases with age and heavy smoking (≥15 cigarettes/day), especially in women over 35.
| Serious Effects |
["Current or history of venous thromboembolism (VTE) or arterial thrombosis","Cerebrovascular disease or coronary artery disease","Thrombogenic valvular or rhythm disorders (e.g., atrial fibrillation)","Major surgery with prolonged immobilization","Diabetes with vascular involvement","Uncontrolled hypertension (BP >160/100 mm Hg)","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","Current or history of migraine with aura (if age ≥35 years or other risk factors)","Cigarette smoking in women over 35 years old","Hypersensitivity to any component of NuvaRing"]
| Precautions | ["Cardiovascular risk: increased risk of venous thromboembolism, stroke, myocardial infarction, especially in smokers and women with hypertension.","Carcinoma: possible increase in breast cancer risk; do not use in women with known or suspected breast cancer.","Hepatic disease: discontinue if jaundice develops; do not use in acute viral hepatitis or severe cirrhosis.","Hypertension: discontinue if blood pressure rises significantly.","Gallbladder disease: possible increased risk.","Carbohydrate/lipid metabolism: monitor glucose in diabetics; may increase triglycerides.","Headache: discontinue if new/worsening migraine or severe headache with neurological symptoms.","Bleeding irregularities: may cause breakthrough bleeding or amenorrhea; rule out pregnancy if withdrawal bleed absent.","Ocular effects: discontinue if unexplained vision loss, proptosis, or papilledema.","Depression: discontinue if significant depression occurs."] |
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| No routine monitoring required as drug is contraindicated during pregnancy. For accidental exposure, monitor for fetal anomalies via ultrasound. |
| Fertility Effects | Post-use fertility return may be delayed, but no permanent impairment. Some studies suggest a temporary increase in time to pregnancy. |