norethindrone acetate (Rx)

Frequency Not Defined

Edema

Weakness

Anorexia

Amenorrhea

Breakthrough bleeding

Change in menstrual flow

Spotting

Deep vein thrombosis

Thrombophlebitis

Depression

Dizziness

Headache

Nervousness

Somnolence

Breast tenderness

Galactorrhea

Abdominal pain

Nausea

Vomiting

Weight change

Cholestatic jaundice

Contraindications

Documented hypersensitivity

Estrogen-dependent neoplasia

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

Estrogen-dependent neoplasia, liver disease, liver tumors

Undiagnosed abnormal vaginal bleeding

Diabetes mellitus with vascular involvement

Jaundice with prior oral contraceptive use

Missed abortion or as diagnostic test for pregnancy

Cautions

Norethindrone acetate is 2 times as potent as norethindrone

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.

Rare hepatic adenomas and focal modular hyperplasia, resulting in fatal intra-abdominal hemorrhage reported with therapy

Irregular menstrual bleeding is common with progestin only contraceptives; rule out nonpharmacologic causes of abnormal bleeding

Not for use prior to menarche

Discontinue 4 week before major surgery or prolonged immobilization. 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.

Pregnancy Category: X

Lactation: Excreted in breast milk; use caution

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 & ovulation, stimulates growth of mammary tissues

Absorption

Bioavailability: 64%

Peak Plasma Time: 1-2 hr

Distribution

Vd: 4 L/kg

Protein Bound: 61%

Metabolism

Liver

Metabolites: Sulfate and glucuronide metabolites (inactive)

Elimination

Half-Life: 4-13 hr

Excretion: Urine 33-81%; feces 35-43%