Dosing and uses of NuvaRing (etonogestrel/ethinylestradiol)
Adult dosage forms and strengths
Etonogestrol/Ethinyl estradioL
vaginal ring
- 0.12mg/0.015mg
Initial Treatment: Previous Contraceptive
No hormonal contraceptive in past month: Insert ring on or before Day 5 (Day 1 being 1st day of menstruation); use additional form of contraception for 7 d;
Combo oral contraceptive: insert ring within 7 d after last active tablet (no later than 1st day new cycle of tablets would begin);
Progestin mini-pill: insert ring on any day of month, on same day as pill is discontinued; do not skip days between the last day and insertion of the ring;
Progestin implant: insert ring on same day of implant removal;
Progestin injection: insert ring on day next inj would be given
Initial Treatment: Post-pregnancy
1st trimester abortion: insert ring within 5 d after abortion
Delivery or 2nd trimester abortion: Insert ring 4 wk later; use additional form of contraception for 7 days
CDC guidelines
- Increased risk for venous thromboembolism (VTE) following delivery with combined hormonal contraceptives; risk declines rapidly after 21 days, but does not return to normal until 42 days after delivery
- CDC guidelines recommend waiting 3-6 weeks in postpartum women without additional VTE risks (MMWR July 7, 2011)
- Initiating after vaginal birth: Wait at least 3 weeks
- Initiating after caesarean section birth: Wait at least 6 weeks
- Women with other risk factors for VTE in addition to postpartum: Do not use combined hormonal contraceptives
If Ring Removed from Vagina
<3 hr: Rinse and reinsert ASAp
>3 hr: Rinse and reinsert ASAP; use additional form of contraception for 7 days
>1 wk: Rule out pregnancy before restarting treatment; use additional form of contraception for 7 days
Administration
If ring left in place >3 wk: remove for 1 wk; rule out pregnancy, then insert new ring; use add'l form of contraception for 7 days
Pediatric dosage forms and strengths
Not recommended
NuvaRing (etonogestrel/ethinylestradiol) adverse (side) effects
>10%
Vaginitis (13.8%)
Headache (including migraine) (11.2%)
1-10%
Mood changes (6.4%)
Device-related events (eg, expulsion/discomfort/foreign body sensation) (6.3%)
Nausea/vomiting (5.9%)
Vaginal discharge (5.7%)
Increased weight (4.9%)
Vaginal discomfort (4%)
Breast pain/discomfort/tenderness (3.8%)
Dysmenorrhea (3.5%)
Abdominal pain (3.2%)
Acne (2.4%)
Decreased libido (2%)
Postmarketing Reports
Immune system disorders: Hypersensitivity
Nervous system disorders: Stroke/cerebrovascular accident
Vascular disorders: Arterial events (including arterial thromboembolism and myocardial infarction), aggravation of varicose veins
Skin and subcutaneous tissue disorders: urticaria, chloasma
Reproductive system and breast disorders: penile disorders, including local reactions on penis (in male partners of women using NuvaRing), galactorrhea
Warnings
Black box warnings
Cigarette smoking & risk of cardiovascular disease
- Cigarette smoking increases risk of serious cardiovascular adverse effects from combination hormonal contraceptive use
- This risk increases with age (>35 yr) & with heavy smoking (15 or more cigarettes/day)
- Advise women who use hormonal oral contraceptives not to smoke
Contraindications
Documented hypersensitivity
Arterial thromboembolic disease (stroke, MI), thrombophlebitis, DVT/PE, thrombogenic valvular disease
Estrogen-dependent neoplasia (current or history of)
Cerebrovascular disease, coronary artery disease
Headaches with focal neurological symptoms
Liver disease, liver tumors
Undiagnosed abnormal vaginal bleeding
Uncontrolled hypertension
Women >35 years who smoke
Major surgery with prolonged immobilization
Diabetes mellitus with vascular involvement, jaundice with prior oral contraceptive use
Cautions
Avoid using diaphragm concomitantly; may interfere with ring placement
Family history of breast cancer and or DVT/Pe
Current/history of depression, endometriosis, DM, HTN, bone mineral density changes, renal/hepatic impairment, bone metabolic disease, SLE; conditions exacerbated by fluid retention (eg, migraine, asthma, epilepsy)
Discontinue if the following develop jaundice, visual problems (may cause contact lens intolerance), any signs of VTE, migraine with unusual severity, significang blood pressure increase, severe depression, increased risk of thromboembolic complications after surgery
Discontinue 4 week before major surgery or prolonged immobilization
Discontinue if an arterial thrombotic or venous thromboembolic event occurs
Estrogens may cause retinal vascular thrombosis; discontinue therapy if visual disturbances occur including migraine, loss of vision, diplopia, or proptosis
Patients on warfarin, oral anticoagulants (increase in anticoagulant dose may be warranted)
Some studies link OCP use with increased risk of breast cancer, whereas other studies have not shown a change in risk; woman's risk depends on conditions where naturally high hormone levels persist for long periods of time including early onset menstruation before age 12, late onset menopause, after age 55, first child after age 30, nulliparity
Increased risk of cervical cancer with OCP use, however HPV remains as main risk factor for this cancer, evidence suggests long-term use of OCPs, 5 or more years, may be associated with increased risk
Increased risk of liver cancer with OCP use; risk increases with longer duration of OCP use
Combination of hormonal contraceptives may affect lipoprotein levels and serum triglycerides
Increased risk of gallbladder disease reported (dose dependent)
Use caution in patients with diseases that may be exacerbated by fluid retention including migraine, diabetes, renal dysfunction, and epilepsy
CDC guidelines recommend waiting at least 3 weeks following vaginal birth or 6 weeks after cesarean section to decrease risk for venous thromboembolism before initiating combined hormonal contraceptives; women with additional risk factors for VTE (besides postpartum) should not use combined hormonal contraceptives (MMWR July 7, 2011)
Pregnancy and lactation
Pregnancy category: X
Lactation: Small amounts of steroids are excreted in breast milk; estrogens may reduce quality/quantity of milk; may be prudent to use other forms of birth control until full weaning (AAP Committee states compatible w/ nursing)
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of NuvaRing (etonogestrel/ethinylestradiol)
Mechanism of action
Ethinyl estradiol (EE): Reduces LHRH release from hypothalamus, reduces gonadotropin release from pituitary; increases synthesis of DNA, RNA, & various proteins in target tissues
Etonogestrel: Progestin; inhibits gonadotropin secretion from pituitary; prevents follicular maturation & ovulation, stimulates growth of mammary tissues
Pharmacokinetics
Half-life: 44.7 hr (ethinyl estradiol); 29.3 hr (etonogestrel)
Excretion: Urine, bile, and feces (ethinyl estradiol and etonogestrel)
Bioavailability: 56% (ethinyl estraiol); 100% (etonogestrel)
Metabolism: Liver (ethinyl estradiol and etonogestrel form metabolites)
Protein binding 98% (ethinyl estradiol); 32% (etonogestrel; sex hormone binding globulin and 66% to albumin)
Absorption: Rapid (ethinyl estradiol and etonogestrel; tampons do not interfere with absorption)
Duration: Serum levels decrease after 3 weeks of continuous use
