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

Contraindications

Documented hypersensitivity

Active or history of breast cancer

Arterial thromboembolic disease (stroke, MI), thrombophlebitis, DVT/PE, thrombogenic valvular disease

Estrogen-dependent neoplasia, liver disease, liver tumors

Undiagnosed abnormal vaginal bleeding

Uncontrolled hypertension

Diabetes mellitus with vascular involvement

Jaundice with prior oral contraceptive use

Hypersensitivity to etonogestrel or component of the formulation

Current/history of thrombophlebitis, thromboembolic disorders

Missed abortion

Cautions

Caution in 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, severe depression, increased risk of thromboembolic complications after surgery.

May cause retinal vascular thrombosis; discontinue if loss of vision, migraine proptosis, diplopia or other visual disturbances occur

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

Increased risk of liver cancer with OCP use; risk increases with longer duration of OCP use

Be alert to the possibility of an ectopic pregnancy in women receiving therapy who become pregnant or complain of lower abdominal pain

Counsel women regarding changes in bleeding frequency, intensity, or duration

Implant should be removed in the event of a thrombosis

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

Monitor prediabetic and diabetic women receiving therapy

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, 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