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Pronunciation
(nor ETH in drone)
Generic Available (U.S.)
Yes
Index Terms
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Treatment of amenorrhea; abnormal uterine bleeding; endometriosis; prevention of pregnancy
Pregnancy Risk Factor
X
Pregnancy Considerations
First trimester exposure may cause genital abnormalities including hypospadias in male infants and mild virilization of external female genitalia. Significant adverse events related to growth and development have not been observed (limited studies). Use is contraindicated during pregnancy. May be started immediately postpartum if not breast-feeding.
Lactation
Enters breast milk/use caution
Breast-Feeding Considerations
Small amounts of progestins are found in breast milk (1% to 6% of maternal serum concentration). Norethindrone can cause changes in milk production in the mother. When used for contraception, may start 3 weeks after delivery in women who are partially breast-feeding, or 6 weeks after delivery in women who are fully breast-feeding.
Contraindications
Hypersensitivity to norethindrone or any component of the formulation; history of or current thrombophlebitis or venous thromboembolic disorders (including DVT, PE); hepatic dysfunction or tumor; known or suspected breast carcinoma; undiagnosed vaginal bleeding; pregnancy; missed abortion or as a diagnostic test for pregnancy
Warnings/Precautions
Concerns related to adverse effects:
• Bleeding: Irregular menstrual bleeding patterns are common with progestin only contraceptives; nonpharmacologic causes of abnormal bleeding should be ruled out.
• Breast cancer: The use of combination hormonal contraceptives has been associated with a slight increase in the frequency of breast cancer, however studies are not consistent. Data is insufficient to determine if progestin only contraceptives also increase this risk.
• Carbohydrate intolerance: May have adverse effects on glucose tolerance; use caution in women with diabetes.
• Lipid effects: May have adverse effects on lipid metabolism; use caution in women with hyperlipidemias.
• Retinal vascular lesions: Progestin use has been associated with retinal vascular lesions; discontinue pending examination in case of sudden vision loss, complete loss of vision, sudden onset of proptosis, diplopia, or migraine.
• Thromboembolism: Use caution in patients at increased risk of thromboembolism; includes elective surgery associated with an increased risk of thromboembolism or during periods of prolonged immobilization.
Disease-related concerns:
• Depression: Use with caution in patients with depression.
• Diseases exacerbated by fluid retention: Use with caution in patients with diseases which may be exacerbated by fluid retention, including asthma, epilepsy, migraine, cardiac or renal dysfunction.
• Hepatic adenomas: Extremely rare hepatic adenomas and focal nodular hyperplasia resulting in fatal intra-abdominal hemorrhage have been reported in association with long-term combination oral contraceptive use. Data is insufficient to determine if progestin-only contraceptives also increase this risk.
• Migraine: Use with caution in patients with a history of migraine.
Special populations:
• Pediatrics: Not for use prior to menarche.
• Smokers: The risk of cardiovascular side effects increases in women using estrogen containing combined hormonal contraceptives and who smoke cigarettes, especially those who are >35 years of age. This risk relative to progestin-only contraceptives has not been established.
Other warnings/precautions:
• HIV infection protection: Progestin-only contraceptives do not protect against HIV infection or other sexually-transmitted diseases.
Adverse Reactions
Frequency not defined.
Cardiovascular: Cerebral embolism, cerebral thrombosis, DVT, edema
Central nervous system: Depression, dizziness, headache, insomnia, migraine, mood swings
Dermatologic: Acne, chloasma, hirsutism, melasma, pruritus, rash, urticaria
Endocrine & metabolic: Amenorrhea, breakthrough bleeding, breast enlargement/tenderness, menstrual flow changes, spotting
Gastrointestinal: Nausea, weight gain/loss
Genitourinary: Cervical erosion changes, cervical secretion changes
Hepatic: Cholestatic jaundice, liver function test abnormalities
Ocular: Optic neuritis (with or without vision loss), retinal vascular thrombosis
Respiratory: Pulmonary embolism
Miscellaneous: Anaphylactic/anaphylactoid reactions
Metabolism/Transport Effects
Substrate of CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Induces CYP2C19 (weak/moderate)
Drug Interactions
Acitretin: May diminish the therapeutic effect of Contraceptives (Progestins). Contraceptive failure is possible. Management: Given the potential for progestin-only preparations to fail to prevent pregnancy during acitretin therapy, such products should not be relied upon. Alternative, nonhormonal forms of contraception must be employed during acitretin therapy. Risk D: Consider therapy modification
Aminoglutethimide: May increase the metabolism of Progestins. Management: Progestin-containing contraceptives are not recommended; consider the use of alternative, nonhormonal contraceptives. Risk D: Consider therapy modification
Aprepitant: May decrease the serum concentration of Contraceptives (Progestins). Management: Alternative or additional methods of contraception should be used both during treatment with aprepitant or fosaprepitant and for at least one month following the last aprepitant/fosaprepitant dose. Risk D: Consider therapy modification
Artemether: May decrease the serum concentration of Contraceptives (Progestins). Management: Consider the use of an alternative (i.e., non-hormonal) means of contraception in all women of childbearing potential who are using artemether. Risk D: Consider therapy modification
Barbiturates: May diminish the therapeutic effect of Contraceptives (Progestins). Contraceptive failure is possible. Management: Use of alternative, nonhormonal contraceptives is recommended. Risk D: Consider therapy modification
Benzodiazepines (metabolized by oxidation): Contraceptives (Progestins) may increase the serum concentration of Benzodiazepines (metabolized by oxidation). Risk C: Monitor therapy
Bexarotene: May decrease the serum concentration of Contraceptives (Progestins). Management: Women of childbearing potential receiving bexarotene should use two reliable forms of contraception (including at least one nonhormonal form). Risk D: Consider therapy modification
Bexarotene (Systemic): May decrease the serum concentration of Contraceptives (Progestins). Management: Women of childbearing potential receiving bexarotene should use two reliable forms of contraception (including at least one nonhormonal form). Risk D: Consider therapy modification
Bile Acid Sequestrants: May decrease the serum concentration of Contraceptives (Progestins). Management: Administer oral progestin-containing contraceptives at least 1-4 hours prior to or 4-6 hours after administration of a bile acid sequestrant. Risk D: Consider therapy modification
Boceprevir: May increase the serum concentration of Contraceptives (Progestins). Management: Do not rely on systemic hormonal contraceptives for contraception during treatment with boceprevir. Patients receiving combination regimens containing ribavirin should use two alternative effective means of contraception. Risk D: Consider therapy modification
Bosentan: May decrease the serum concentration of Contraceptives (Progestins). Management: Use an alternative (i.e., non-hormonal) means of contraception for all women of childbearing potential who are using bosentan, and do not rely on hormonal contraceptives alone. Risk D: Consider therapy modification
CarBAMazepine: May diminish the therapeutic effect of Contraceptives (Progestins). Contraceptive failure is possible. Management: Use of alternative, nonhormonal contraceptives is recommended. Risk D: Consider therapy modification
Clobazam: May decrease the serum concentration of Contraceptives (Progestins). Risk D: Consider therapy modification
Colesevelam: May decrease the serum concentration of Norethindrone. Risk D: Consider therapy modification
Conivaptan: May increase the serum concentration of CYP3A4 Substrates (Low risk). Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
Darunavir: May decrease the serum concentration of Norethindrone. Risk D: Consider therapy modification
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Felbamate: May decrease the serum concentration of Contraceptives (Progestins). Management: Contraceptive failure is possible. Use of an alternative, nonhormonal method of contraception is recommended. Risk D: Consider therapy modification
Fosaprepitant: May decrease the serum concentration of Contraceptives (Progestins). The active metabolite aprepitant is likely responsible for this effect. Management: Alternative or additional methods of contraception should be used both during treatment with aprepitant or fosaprepitant and for at least one month following the last aprepitant/fosaprepitant dose. Risk D: Consider therapy modification
Fosphenytoin: May diminish the therapeutic effect of Contraceptives (Progestins). Contraceptive failure is possible. Management: Contraceptive failure is possible. Use of an alternative, nonhormonal contraceptive is recommended. Risk D: Consider therapy modification
Griseofulvin: May diminish the therapeutic effect of Contraceptives (Progestins). Contraceptive failure is possible. Risk X: Avoid combination
Herbs (Progestogenic Properties) (eg, Bloodroot, Yucca): May enhance the adverse/toxic effect of Progestins. Risk C: Monitor therapy
LamoTRIgine: May decrease the serum concentration of Contraceptives (Progestins). Management: Women using progestin-only “minipill” products may be at risk for contraceptive failure; it is unclear if other progestin-containing products would be significantly impacted. Alternative, non-hormonal, means of contraception are recommended. Risk D: Consider therapy modification
Mycophenolate: May decrease the serum concentration of Contraceptives (Progestins). Management: Use of an additional or alternative (nonhormonal) method of contraception should be considered. Risk D: Consider therapy modification
Nevirapine: May decrease the serum concentration of Contraceptives (Progestins). Management: Instruct patients receiving nevirapine to use an alternative or additional nonhormonal contraceptive. Nevirapine product labeling however suggests that depo-medroxyprogesterone acetate may be used as a sole method of contraception. Risk D: Consider therapy modification
OXcarbazepine: May decrease the serum concentration of Contraceptives (Progestins). Management: Contraceptive failure is possible. Use of an additional or alternative, nonhormonal method of contraception is recommended. Risk D: Consider therapy modification
Phenytoin: May diminish the therapeutic effect of Contraceptives (Progestins). Contraceptive failure is possible. Management: Contraceptive failure is possible. Use of an alternative, nonhormonal contraceptive is recommended. Risk D: Consider therapy modification
Prucalopride: May decrease the serum concentration of Contraceptives (Progestins). Risk D: Consider therapy modification
Retinoic Acid Derivatives: May diminish the therapeutic effect of Contraceptives (Progestins). Retinoic Acid Derivatives may decrease the serum concentration of Contraceptives (Progestins). Management: Two forms of effective contraception should be used in patients receiving retinoic acid derivatives. Particularly, microdosed progesterone-only preparations may be inadequately effective. Risk D: Consider therapy modification
Rifamycin Derivatives: May decrease the serum concentration of Contraceptives (Progestins). Contraceptive failure is possible. Management: Contraceptive failure is possible. Use of an alternative, nonhormonal contraceptive is recommended. Risk D: Consider therapy modification
Rufinamide: May decrease the serum concentration of Norethindrone. Risk D: Consider therapy modification
Selegiline: Contraceptives (Progestins) may increase the serum concentration of Selegiline. Risk C: Monitor therapy
St Johns Wort: May diminish the therapeutic effect of Contraceptives (Progestins). Contraceptive failure is possible. Management: Consider using a product other than St John's wort. Contraceptive failure is possible. Use of an alternative, nonhormonal contraceptive is recommended. Risk D: Consider therapy modification
Telaprevir: May decrease the serum concentration of Contraceptives (Progestins). Management: Two different nonhormonal forms of contraception are required for women of childbearing potential taking telaprevir. Hormonal contraceptives may be less effective during concurrent telaprevir and for up to 2 weeks after telaprevir discontinuation. Risk D: Consider therapy modification
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Topiramate: May decrease the serum concentration of Contraceptives (Progestins). Management: Caution patients that this combination may be associated with reduced contraceptive effectiveness. Consider adding an additional (non-hormonal) contraceptive method. Risk D: Consider therapy modification
Tranexamic Acid: Contraceptives (Progestins) may enhance the thrombogenic effect of Tranexamic Acid. Management: Ensure that the potential benefits of concurrent therapy outweigh the increased risk of potential thrombosis that accompanies use of tranexamic acid with hormonal contraceptives. Risk D: Consider therapy modification
Vitamin K Antagonists (eg, warfarin): Contraceptives (Progestins) may diminish the anticoagulant effect of Vitamin K Antagonists. In contrast, enhanced anticoagulant effects have also been noted with some products. Management: When possible, concomitant hormonal contraceptives and coumarin derivatives should be avoided in order to eliminate the risk of thromboembolic disorders. Consider using an alternative, nonhormonal contraceptive. Risk D: Consider therapy modification
Voriconazole: May increase the serum concentration of Contraceptives (Progestins). Contraceptives (Progestins) may increase the serum concentration of Voriconazole. Risk C: Monitor therapy
Ethanol/Nutrition/Herb Interactions
Herb/Nutraceutical: Avoid bloodroot, chasteberry, damiana, oregano, and yucca; may enhance the adverse/toxic effect of progestins. Avoid St John's wort; may diminish the therapeutic effect of progestin contraceptives; contraceptive failure is possible.
Storage
Store at controlled room temperature of 25°C (77°F).
Mechanism of Action
Inhibits secretion of pituitary gonadotropin (LH) which prevents follicular maturation and ovulation
Pharmacodynamics/Kinetics
Absorption: Oral: Rapidly absorbed
Distribution: Vd: 4 L/kg
Protein binding: 61% to albumin; 36% to sex hormone-binding globulin (SHBG); SHBG capacity affected by plasma ethinyl estradiol levels
Metabolism: Oral: Hepatic via reduction and conjugation; first-pass effect
Bioavailability: 64%
Half-life elimination: ~8 hours
Time to peak: 1-2 hours
Excretion: Urine (>50% as metabolites); feces (20% to 40% as metabolites)
Dosage
Oral: Adolescents and Adults: Females:
Contraception: Progesterone only: Norethindrone 0.35 mg every day (no missed days)
Initial dose: Start on first day of menstrual period or the day after a miscarriage or abortion. If switching from a combined oral contraceptive, begin the day after finishing the last active combined tablet.
Missed dose: Take as soon as remembered. A back up method of contraception should be used for 48 hours if dose is taken ≥3 hours late.
Amenorrhea and abnormal uterine bleeding: Norethindrone acetate: 2.5-10 mg/day for 5-10 days during the second half of the menstrual cycle
Endometriosis: Norethindrone acetate: 5 mg/day for 14 days; increase at increments of 2.5 mg/day every 2 weeks to reach 15 mg/day; continue for 6-9 months or until breakthrough bleeding demands temporary termination
Administration: Oral
Administer at the same time each day. When used for the prevention of pregnancy, a back up method of contraception should be used for 48 hours if dose is missed or taken ≥3 hours late.
Monitoring Parameters
Contraception: Before starting therapy, a physical exam with reference to the breasts and pelvis are recommended, including a Papanicolaou smear. Exam may be deferred if appropriate; pregnancy should be ruled out prior to use. Monitor patient closely for loss of vision, sudden onset of proptosis, diplopia, migraine; blood pressure; signs and symptoms of thromboembolic disorders; signs or symptoms of depression; glycemic control in patients with diabetes; lipid profiles in patients being treated for hyperlipidemias. Adequate diagnostic measures, including endometrial sampling, if indicated, should be performed to rule out malignancy in all cases of undiagnosed abnormal vaginal bleeding.
Test Interactions
May increase prothrombin, factors VII, VIII, IX, and X, PBI, and BEI. May decrease T3 uptake; may decrease sex hormone-binding globulin (SHBG); may have a reduced response to metyrapone test.
Dietary Considerations
Should be taken at same time each day.
Patient Education
Take according to prescribed schedule. Follow instructions for regular self-breast exam. You may experience dizziness or lightheadedness. Limit intake of caffeine. Avoid high-dose vitamin C. If you have diabetes, monitor blood glucose closely. You may experience photosensitivity, loss of hair (reversible), swelling of hands or feet, or weight gain or loss. Report sudden severe headache or vomiting; disturbances of vision or speech; sudden blindness; numbness or weakness in an extremity; chest pain; calf pain; respiratory difficulty; weight gain; depression or acute fatigue; or unusual bleeding, spotting, or changes in menstrual flow.
Dental Health: Effects on Dental Treatment
Until we know more about the mechanism of interaction, caution is required in prescribing antibiotics to female dental patients taking progestin-only hormonal contraceptives.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May cause insomnia or depression
Mental Health: Effects on Psychiatric Treatment
None reported
Nursing: Physical Assessment/Monitoring
Teach appropriate administration schedule. Schedule physical exam with reference to the breasts and pelvis, including a Papanicolaou smear. Exam may be deferred if appropriate; pregnancy should be ruled out prior to use. Monitor patient closely for loss of vision, sudden onset of proptosis, diplopia, migraine, blood pressure, signs and symptoms of thromboembolic disorders, signs or symptoms of depression, glycemic control in diabetics, and lipid profiles in patients being treated for hyperlipidemias. Adequate diagnostic measures, including endometrial sampling, if indicated, should be performed to rule out malignancy in all cases of undiagnosed abnormal vaginal bleeding. Emphasize need for regular breast self-exam and necessity of annual physical check-up with long-term use.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, oral: 0.35 mg
Camila®: 0.35 mg
Errin®: 0.35 mg
Heather: 0.35 mg
Jolivette®: 0.35 mg
Nor-QD®: 0.35 mg
Nora-BE®: 0.35 mg
Ortho Micronor®: 0.35 mg
Tablet, oral, as acetate: 5 mg
Aygestin®: 5 mg [scored]
Pricing: U.S. (www.drugstore.com)
Tablets (Aygestin)
5 mg (30): $104.98
Tablets (Camila)
0.35 mg (28): $34.99
Tablets (Jolivette)
0.35 mg (28): $35.99
Tablets (Nor-QD)
0.35 mg (28): $71.99
Tablets (Nora-BE)
0.35 mg (28): $33.99
Tablets (Norethindrone Acetate)
5 mg (30): $76.99
References
American College of Obstetricians and Gynecologists, “ACOG Committee Opinion. Number 310, April 2005. Endometriosis in Adolescents,” Obstet Gynecol, 2005, 105(4):921-7.
ACOG Committee on Practice Bulletins-Gynecology, “ACOG Practice Bulletin. No. 73: Use of Hormonal Contraception in Women With Coexisting Medical Conditions,” Obstet Gynecol, 2006, 107(6):1453-72.
International Brand Names
Lexi-Comp.com
Last full review/revision March 2012
Content last modified March 2012
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