etonogestrel (Rx)

>10%

Oligomenorrhea (34%)

Headache (25%)

Vaginitis (24.5%)

Amenorrhea (22%)

Menorrhagia (18%)

Weight gain (14%)

Acne (13.5%)

Breast pain (13%)

Upper resp tract infection (13%)

Pharyngitis (11%)

Leucorrhea (10.5%)

1-10%

Back pain (7%)

Depression (6%)

Dizziness (7%)

Dysmenorrhea (7%)

Emotional lability (7%)

Flu-like symptoms (8%)

Insertion-site pain (9%)

Nausea (6%)

Nervousness (6%)

Pain (6%)

Postmarketing Reports

Gastrointestinal disorders: Constipation, diarrhea, flatulence, vomiting

General disorders and administration site conditions: Edema, fatigue, implant site reaction, pyrexia

Immune system disorders: Anaphylactic reactions

Infections and infestations: rhinitis, urinary tract infection

Investigations: Clinically relevant rise in blood pressure, weight decreased

Metabolism and nutrition disorders: Increased appetite

Musculoskeletal and connective tissue disorders: Arthralgia, musculoskeletal pain, myalgia

Nervous system disorders: Convulsions, migraine, somnolence

Pregnancy, puerperium and perinatal conditions: Ectopic pregnancy

Psychiatric disorders: Anxiety, insomnia, libido decreased

Renal and urinary disorders: Dysuria

Reproductive system and breast disorders: Breast discharge, breast enlargement, ovarian cyst, pruritus genital, vulvovaginal discomfort

Skin and subcutaneous tissue disorders: Angioedema, aggravation of angioedema and/or aggravation of hereditary angioedema, alopecia, chloasma, hypertrichosis, pruritus, rash, seborrhea, urticaria

Vascular disorders: Hot flush; chest pain and/or respiratory disorders (such as dyspnea, cough, or hemoptysis when implants found within pulmonary artery)

Contraindications

Documented hypersensitivity

Known or suspected breast cancer, personal history of breast cancer, or other progestin-sensitive cancer, now or in the past

Liver tumors, benign or malignant, or active liver disease

Undiagnosed abnormal vaginal bleeding

Hypersensitivity to etonogestrel or component of the formulation

Current/history of thrombophlebitis, thromboembolic disorders

Cautions

Caution in family history of 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)

Women with family history of breast cancer or who develop breast nodules should be carefully monitored

Due to risk of thromboembolism associated with pregnancy and immediately following delivery, drug should not be used prior to 21 days postpartum; women with history of thromboembolic disorders should be made aware of possibility of recurrence

Discontinue if the following develop jaundice, visual problems (may cause contact lens intolerance), any signs of VTE, migraine with unusual severity, severe depression, increased risk of thromboembolic complications after surgery

Contact lens wearers who develop visual changes or changes in lens tolerance should be assessed by an ophthalmologist

Evaluate for retinal vein thrombosis immediately if there is unexplained loss of vision, proptosis, diplopia, papilledema, or retinal vascular lesions

Discontinue 4 week before major surgery or prolonged immobilization

Use caution in 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

Hormonal contraceptives may cause some degree of fluid retention; prescribe with caution, and only with careful monitoring, in patients with conditions which might be aggravated by fluid retention; unknown if drug causes fluid retention

Disturbances of liver function may necessitate discontinuation of hormonal contraceptive use until markers of liver function return to normal; remove treatment if jaundice develops; progestin may be poorly metabolized in women with liver impairment; increased risk of liver cancer with OCP use; risk increases with longer duration of OCP use

A pregnancy that occurs in a woman may be more likely to be ectopic than a pregnancy occurring in a woman using no contraception; be alert to possibility of ectopic pregnancy in women receiving therapy who become pregnant or complain of lower abdominal pain

After starting therapy, women are likely to have a change from their normal menstrual bleeding pattern; these may include changes in bleeding frequency (absent, less, more frequent or continuous), intensity (reduced or increased) or duration; evaluate abnormal bleeding as needed to exclude pathologic conditions or pregnancy

Implant should be removed in the event of a thrombosis

Discourage women with history of hypertension-related diseases or renal disease from using hormonal contraception; women with well-controlled hypertension, use can be considered; women with hypertension receiving therapy should be closely monitored; if sustained hypertension develops during therapy, or if a significant increase in blood pressure does not respond adequately to antihypertensive therapy, remove implant

Patient receiving therapy should have a yearly visit with healthcare provider for a blood pressure check and for other indicated health care

Implant should be removed if blood pressure rises significantly and becomes uncontrolled

When implant broken or bent, may increase release rate of etonogestrel; when implant removed, remove it in its entirety

Small increased relative risk of developing gallbladder disease among combination hormonal contraceptive users reported; not known whether a similar risk exists with progestin-only methods

Monitor prediabetic and diabetic women receiving therapy; may induce mild insulin resistance and small changes in glucose concentrations of unknown clinical significance; carefully monitor prediabetic and diabetic women receiving therapy

Follow closely women being treated for hyperlipidemia, if they elect to receive treatment; some progestins may elevate LDL levels and may render control of hyperlipidemia more difficult

If follicular development occurs, atresia of follicle is sometimes delayed, and follicle may continue to grow beyond size it would attain in normal cycle; generally, enlarged follicles disappear spontaneously; on rare occasion, surgery may be required

Sex hormone-binding globulin concentrations may be decreased for first six months after implant insertion followed by gradual recovery; thyroxine concentrations may initially be slightly decreased followed by gradual recovery to baseline

Re-start contraception immediately after removal of implant if continued contraceptive protection is desired

Complications of Insertion

• Implant removal may be difficult or impossible if implant not inserted correctly, inserted too deeply, not palpable, encased in fibrous tissue, or has migrated
• Exploratory surgery without knowledge of exact location of implant is strongly discouraged
• Migration of implant within arm from insertion site, which may be related to deep insertion, reported; in cases where implant has migrated to pulmonary artery, chest pain and/or respiratory disorders (such as dyspnea, cough, or hemoptysis) reportred; others were asymptomatic; endovascular or surgical procedures may be needed for removal
• If at any time implant cannot be palpated, it should be localized; removal is recommended
• If inserted deeply (intramuscular or in fascia), neural or vascular injury may occur; to help reduce risk of neural or vascular injury insert product subdermally just under skin at inner side of non-dominant upper arm overlying the triceps muscle about 8-10 cm (3-4 inches) from medial epicondyle of humerus and 3-5 cm (1.25-2 inches) posterior to sulcus (groove) between biceps and triceps muscles; this location avoids large blood vessels and nerves lying within and surrounding the sulcus

Pregnancy

Contraindicated during pregnancy because there is no need for pregnancy prevention in woman who is already pregnant; epidemiologic studies and meta-analyses have not shown an increased risk of genital or non-genital birth defects (including cardiac anomalies and limb-reduction defects) following maternal exposure to low dose CHCs prior to conception or during early pregnancy

Lactation

Small amounts of contraceptive steroids and/or metabolites, including etonogestrel are present in human milk; no significant adverse effects observed in production or quality of breast milk, or on physical and psychomotor development of breastfed infants

Hormonal contraceptives, including etonogestrel, can reduce milk production in breastfeeding mothers; this is less likely to occur once breastfeeding is well-established; however, it can occur at any time in some women; when possible, advise nursing mother about both hormonal and non-hormonal contraceptive options, as steroids may not be initial choice for these patients; developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for hormonal contraceptive and any potential adverse effects on breastfed child from hormonal contraceptive or from underlying maternal condition

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.

Mechanism of Action

Progestin; inhibits secretion of gonadotropins from pituitary gland; prevents follicular maturation and ovulation, increases viscosity of cervical mucous, and stimulates growth of mammary tissues

Absorption

Bioavailability: 100%

Release Rate

• Week 5-6: 60-70 mcg/day
• After 1 yr: 35-45 mcg/day
• After 2 yr: 30-40 mcg/day
• After 3 yr: 25-30 mcg/day

Distribution

Protein Bound: 98% (32% SHBG; 66% albumin)

Vd: 201 L

Metabolism

Hepatic CYP3A4

Elimination

Half-Life: 25 hr

Excretion: Urine (primarily), feces