What is the dosing regimen for norethindrone in a female patient of reproductive age?

Norethindrone Dosing Regimens

Norethindrone dosing varies significantly by indication: for contraception use 0.35 mg daily continuously without breaks; for menstrual delay use 5 mg two to three times daily starting 3 days before expected menses; and for hormone replacement therapy use 0.5-1.0 mg daily for 12-14 days per month in sequential regimens or minimum 1 mg daily for continuous regimens. 1, 2, 3

Contraceptive Dosing

• Take 0.35 mg orally once daily at the same time every day without any interruption between pill packs 4, 3
• Administration must be continuous with no pill-free intervals, as progestin-only pills have a shorter half-life than combined hormonal contraceptives 4
• When transitioning from combined hormonal contraceptives, start norethindrone on the first day of withdrawal bleeding to maintain continuous contraceptive protection 4
• This timing maintains suppressed ovarian activity and reduces irregular bleeding risk 4
• Drug effectiveness rate is 1.9 pregnancies per 100 woman-years with regular use 5

Menstrual Delay Dosing

• Use 5 mg orally two to three times daily, starting 3 days before the expected period 2
• Continue until menstruation is desired, then stop to allow withdrawal bleeding 2
• This is NOT a contraceptive method—additional contraception is required if sexually active 2
• The full 5 mg dose 2-3 times daily is necessary for reliable menstrual suppression 2

Hormone Replacement Therapy Dosing

Sequential Regimens

• Use 10 mg daily for 12-14 days per month when combined with estrogen therapy 1, 6
• This dosing induces regular withdrawal bleeding with secretory endometrial transformation 6

Continuous Regimens

• Minimum dose of 1 mg daily when used continuously with estrogen 1
• Doses of 0.5-1.0 mg daily have been studied with transdermal estradiol, all providing adequate endometrial protection 6

Combined Oral Contraceptive Formulations

• Norethindrone acetate 1 mg/ethinyl estradiol 20 mcg: Take 1 pill daily for 24 days followed by 4 days of placebo 7
• The 24-day active regimen reduces intracyclic bleeding compared to 21-day regimens (0.95 vs 1.63 days, p=0.005) 7
• Norethindrone with ethinyl estradiol: Take 1 pill daily for 21 days followed by 7 days off 1
• Only recommended for post-menarchal females aged 15 years and older 1

Critical Safety Considerations

Absolute Contraindications

• Pregnancy, active or history of arterial thromboembolic disease, breast cancer or hormone-sensitive cancers 1, 2, 4
• Undiagnosed vaginal bleeding, active liver disease or hepatic tumors 1, 2, 4
• History of deep vein thrombosis or thromboembolic disease 1, 2, 4
• Uncontrolled hypertension 2, 4

Drug Interactions

• When taking rifamycins (rifampin, rifabutin, rifapentine), add barrier contraception as rifamycins substantially decrease norethindrone levels 8
• This interaction applies to all hormonal contraceptives containing norethindrone 8

Common Pitfalls

• Timing precision is critical for the 0.35 mg contraceptive dose—even small delays reduce efficacy due to short half-life 4, 3
• Do not use norethindrone repeatedly for menstrual delay; consider alternative hormonal management for frequent use 2
• Perform pregnancy testing if withdrawal bleeding does not occur before starting norethindrone 4
• Breakthrough bleeding occurs more commonly with progestin-only pills but can be minimized by strict adherence to timing 4
• Norethindrone is not suitable for pre-menarchal patients—safety and efficacy are not established 1