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standards of non-Merck sources.
Medication Safety Issues
Sound-alike/look-alike issues:
Micronor® may be confused with miconazole, Micronase®
Pronunciation
(nor ETH in drone)
U.S. Brand Names
Index Terms
Generic Available
Yes
Canadian Brand Names
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); Induces CYP2C19 (weak)
Drug Interactions
Acitretin: May diminish the therapeutic effect of Contraceptive (Progestins). Contraceptive failure is possible. Risk X: Avoid combination
Aminoglutethimide: May increase the metabolism of Progestins. Risk D: Consider therapy modification
Aprepitant: May decrease the serum concentration of Contraceptive (Progestins). Risk D: Consider therapy modification
Barbiturates: May diminish the therapeutic effect of Contraceptive (Progestins). Contraceptive failure is possible. Risk D: Consider therapy modification
Benzodiazepines (metabolized by oxidation): Oral Contraceptive (Progestins) may decrease the metabolism of Benzodiazepines (metabolized by oxidation). Risk C: Monitor therapy
Carbamazepine: May diminish the therapeutic effect of Contraceptive (Progestins). Contraceptive failure is possible. Risk D: Consider therapy modification
Colesevelam: May decrease the serum concentration of Norethindrone. Risk D: Consider therapy modification
Coumarin Derivatives: Contraceptive (Progestins) may diminish the anticoagulant effect of Coumarin Derivatives. In contrast, enhanced anticoagulant effects have also been noted with some products. Risk D: Consider therapy modification
CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
Felbamate: May decrease the serum concentration of Oral Contraceptive (Progestins). Contraceptive failure is possible. Risk D: Consider therapy modification
Fosaprepitant: May decrease the serum concentration of Contraceptive (Progestins). The active metabolite aprepitant is likely responsible for this effect. Risk D: Consider therapy modification
Griseofulvin: May diminish the therapeutic effect of Contraceptive (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
Mycophenolate: May decrease the serum concentration of Oral Contraceptive (Progestins). Risk D: Consider therapy modification
Oxcarbazepine: May decrease the serum concentration of Oral Contraceptive (Progestins). Contraceptive failure is possible. Risk D: Consider therapy modification
Phenytoin: May diminish the therapeutic effect of Contraceptive (Progestins). Contraceptive failure is possible. Risk D: Consider therapy modification
Retinoic Acid Derivatives: May diminish the therapeutic effect of Oral Contraceptive (Progestins). Two forms of contraception are recommended in females of child-bearing potential during retinoic acid derivative therapy. Exceptions: Adapalene; Alitretinoin; Tretinoin (Topical). Risk C: Monitor therapy
Rifamycin Derivatives: May decrease the serum concentration of Contraceptive (Progestins). Contraceptive failure is possible. Risk D: Consider therapy modification
Selegiline: Oral Contraceptive (Progestins) may increase the serum concentration of Selegiline. Risk D: Consider therapy modification
St Johns Wort: May diminish the therapeutic effect of Contraceptive (Progestins). Contraceptive failure is possible. Risk D: Consider therapy modification
Voriconazole: May decrease the metabolism of Oral Contraceptive (Progestins). Oral Contraceptive (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: Female:
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; use caution when driving or engaging in tasks that require alertness until response to drug is known. Limit intake of caffeine. Avoid high-dose vitamin C. If you have diabetes, monitor blood glucose closely. You may experience photosensitivity; use sunscreen, wear protective clothing and eyewear, and avoid direct sunlight. You may experience loss of hair (reversible), swelling of hands or feet, weight gain or loss. Report sudden severe headache or vomiting, disturbances of vision or speech, sudden blindness, numbness of weakness in an extremity, chest pain, calf pain, respiratory difficulty, weight gain >5 lb/week, depression or acute fatigue, unusual bleeding, spotting, or changes in menstrual flow. Pregnancy/breast-feeding precautions: Inform prescriber if you are pregnant. Consult prescriber if breast-feeding.
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
Assess patient knowledge/teach appropriate administration schedule and adverse signs to report. 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; 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. Teach appropriate breast self-exam and the need for regular breast self-exam and necessity of annual physical check-up with long-term use. Pregnancy risk factor X: Determine that patient is not pregnant before beginning treatment.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet:
Camila™, Errin™, Jolivette™, Ortho Micronor®, Nora-BE™, Nor-QD®: 0.35 mg
Tablet, as acetate:
Aygestin®: 5 mg
Pricing: U.S. (www.drugstore.com)
Tablets (Aygestin)
5 mg (30): $81.24
Tablets (Camila)
0.35 mg (28): $34.99
Tablets (Errin)
0.35 mg (28): $30.99
Tablets (Jolivette)
0.35 mg (28): $33.99
Tablets (Nor-QD)
0.35 mg (28): $60.99
Tablets (Nora-BE)
0.35 mg (28): $33.99
Tablets (Norethindrone Acetate)
5 mg (30): $56.99
Tablets (Ortho Micronor)
0.35 mg (28): $46.99
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 August 2008
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