ORTHO-NOVUM 2-21

Clinical safety rating: caution

Comprehensive clinical and safety monograph for ORTHO-NOVUM 2-21 (ORTHO-NOVUM 2-21).

How it works

Combination of estrogen (ethinyl estradiol) and progestin (norethindrone) inhibits ovulation via negative feedback on the hypothalamic-pituitary-ovarian axis, suppressing gonadotropin release. Additionally, induces changes in cervical mucus and endometrium.

What the body does with it

Metabolism	Ethinyl estradiol is metabolized primarily via CYP3A4, with contributions from CYP2C9 and CYP2C19. Norethindrone is metabolized via CYP3A4 and reduction pathways.
Excretion	Renal (approx. 60% as metabolites), fecal (approx. 40% as metabolites). Norethindrone and ethinyl estradiol are extensively metabolized; less than 5% excreted unchanged in urine.
Half-life	Norethindrone: terminal half-life 5-12 hours; ethinyl estradiol: terminal half-life 7-20 hours (enterohepatic recirculation may prolong effect). Steady-state achieved after 5-7 days.
Protein binding	Norethindrone: ~60% bound to albumin, ~1.5% to SHBG; ethinyl estradiol: ~97% bound to albumin (not to SHBG).
Volume of Distribution	Vd for norethindrone: ~3.1±0.5 L/kg; for ethinyl estradiol: ~3.5–4.5 L/kg. Indicates extensive tissue distribution.
Bioavailability	Oral: norethindrone ~64% (first-pass metabolism reduces it); ethinyl estradiol ~38-48% (high first-pass metabolism).
Onset of Action	Oral: 2-3 days for contraceptive effect (requires 7 consecutive days of dosing to achieve adequate suppression of ovulation).
Duration of Action	24 hours per dose; contraceptive protection maintained if taken daily. Missed pills >12 hours reduce efficacy.

Classification & Brands

Dosing & administration

One tablet orally once daily for 21 days followed by 7 days off. Each tablet contains norethindrone 2 mg and ethinyl estradiol 0.1 mg.

Dosage form	TABLET
Renal impairment	No dosage adjustment required for mild to moderate renal impairment. For severe renal impairment (GFR <30 mL/min) or dialysis, use is not recommended due to potential fluid retention and hypertension.
Liver impairment	Contraindicated in acute or chronic hepatocellular disease with abnormal liver function, including Child-Pugh class B or C. Adjustment not applicable in mild hepatic impairment (Child-Pugh class A) but use caution and monitor.
Pediatric use	Not indicated for use before menarche. After menarche, dosing is same as adult (one tablet daily for 21 days, then 7 days off). Weight-based guidelines are not established.
Geriatric use	Not indicated for postmenopausal women. No specific geriatric dosing adjustments have been studied.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for ORTHO-NOVUM 2-21 (ORTHO-NOVUM 2-21).

Breastfeeding	Contraindicated during breastfeeding due to potential for reduced milk production and excretion of estrogen/progestin into breast milk. M/P ratio: Not established.
Teratogenic Risk	Category X: Contraindicated in pregnancy. First trimester: Increased risk of cardiovascular and limb reduction defects. Second and third trimesters: Associated with feminization of male fetuses and potential for other teratogenic effects.
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

Cigarette smoking increases the risk of serious cardiovascular events from combination oral contraceptive use. Risk increases with age (especially in women over 35) and with heavy smoking (≥15 cigarettes/day). Women who use oral contraceptives should be strongly advised not to smoke.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Thrombophlebitis or thromboembolic disorders (current or history)","Cerebrovascular or coronary artery disease","Known or suspected pregnancy","Undiagnosed abnormal genital bleeding","Known or suspected breast cancer or estrogen-dependent neoplasia","Hepatic adenoma or carcinoma (current or history)","Jaundice or liver disease (acute or chronic)","Hypersensitivity to any component","Smoking in women over 35 (<15 cigarettes/day is relative; >15 is absolute)"]

Clinical Precautions

Precautions

["Thrombotic events (venous and arterial)","Cardiovascular risks in smokers over 35","Hepatic neoplasia","Hypertension","Gallbladder disease","Carbohydrate/lipid metabolism effects","Ocular lesions (retinal thrombosis)","Reduced efficacy with hepatic enzyme inducers"]

Clinical Tips & Counseling

Drug interactions

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ORTHO-NOVUM 2-21

Clinical safety rating: caution

Comprehensive clinical and safety monograph for ORTHO-NOVUM 2-21 (ORTHO-NOVUM 2-21).

How it works

What the body does with it

Metabolism	Ethinyl estradiol is metabolized primarily via CYP3A4, with contributions from CYP2C9 and CYP2C19. Norethindrone is metabolized via CYP3A4 and reduction pathways.
Excretion	Renal (approx. 60% as metabolites), fecal (approx. 40% as metabolites). Norethindrone and ethinyl estradiol are extensively metabolized; less than 5% excreted unchanged in urine.
Half-life	Norethindrone: terminal half-life 5-12 hours; ethinyl estradiol: terminal half-life 7-20 hours (enterohepatic recirculation may prolong effect). Steady-state achieved after 5-7 days.
Protein binding	Norethindrone: ~60% bound to albumin, ~1.5% to SHBG; ethinyl estradiol: ~97% bound to albumin (not to SHBG).
Volume of Distribution	Vd for norethindrone: ~3.1±0.5 L/kg; for ethinyl estradiol: ~3.5–4.5 L/kg. Indicates extensive tissue distribution.
Bioavailability	Oral: norethindrone ~64% (first-pass metabolism reduces it); ethinyl estradiol ~38-48% (high first-pass metabolism).
Onset of Action	Oral: 2-3 days for contraceptive effect (requires 7 consecutive days of dosing to achieve adequate suppression of ovulation).
Duration of Action	24 hours per dose; contraceptive protection maintained if taken daily. Missed pills >12 hours reduce efficacy.

Classification & Brands

Dosing & administration

One tablet orally once daily for 21 days followed by 7 days off. Each tablet contains norethindrone 2 mg and ethinyl estradiol 0.1 mg.

Dosage form	TABLET
Renal impairment	No dosage adjustment required for mild to moderate renal impairment. For severe renal impairment (GFR <30 mL/min) or dialysis, use is not recommended due to potential fluid retention and hypertension.
Liver impairment	Contraindicated in acute or chronic hepatocellular disease with abnormal liver function, including Child-Pugh class B or C. Adjustment not applicable in mild hepatic impairment (Child-Pugh class A) but use caution and monitor.
Pediatric use	Not indicated for use before menarche. After menarche, dosing is same as adult (one tablet daily for 21 days, then 7 days off). Weight-based guidelines are not established.
Geriatric use	Not indicated for postmenopausal women. No specific geriatric dosing adjustments have been studied.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for ORTHO-NOVUM 2-21 (ORTHO-NOVUM 2-21).

Breastfeeding	Contraindicated during breastfeeding due to potential for reduced milk production and excretion of estrogen/progestin into breast milk. M/P ratio: Not established.
Teratogenic Risk	Category X: Contraindicated in pregnancy. First trimester: Increased risk of cardiovascular and limb reduction defects. Second and third trimesters: Associated with feminization of male fetuses and potential for other teratogenic effects.
Fetal Monitoring