Introduction
Junel is a combination oral contraceptive containing ethinyl estradiol and norethindrone acetate. It is a monophasic formulation approved for pregnancy prevention and is also used for menstrual cycle regulation and management of acne in women seeking contraception.
Mechanism of Action
Junel works through three primary mechanisms: inhibition of ovulation via suppression of gonadotropin secretion, alteration of cervical mucus to impede sperm penetration, and modification of the endometrial lining to reduce implantation potential. The estrogen component (ethinyl estradiol) suppresses follicle-stimulating hormone (FSH), while the progestin component (norethindrone acetate) primarily suppresses luteinizing hormone (LH).
Indications
- Prevention of pregnancy
- Treatment of moderate acne vulgaris in females at least 15 years old who have no known contraindications to oral contraceptive therapy, desire contraception, have achieved menarche, and are unresponsive to topical anti-acne medications
- Management of menstrual cycle irregularities (off-label)
Dosage and Administration
Standard regimen: One tablet daily for 21 consecutive days followed by 7 days of placebo, or 24 active tablets followed by 4 placebo tablets depending on the specific formulation. Special populations:- Hepatic impairment: Contraindicated in acute or severe hepatic disease
- Renal impairment: No dosage adjustment required
- Geriatric patients: Not indicated in postmenopausal women
- Adolescents: May be used after menarche
Pharmacokinetics
Absorption: Ethinyl estradiol is rapidly and completely absorbed (bioavailability ~43%). Norethindrone acetate is rapidly hydrolyzed to norethindrone and completely absorbed (bioavailability ~65%). Distribution: Ethinyl estradiol is highly bound to albumin (98.5%). Norethindrone is primarily bound to SHBG and albumin. Metabolism: Hepatic metabolism via cytochrome P450 enzymes (primarily CYP3A4). Ethinyl estradiol undergoes extensive first-pass metabolism and enterophepatic recirculation. Elimination: Ethinyl estradiol elimination half-life ~24 hours. Norethindrone elimination half-life ~8 hours. Excreted primarily in urine and feces.Contraindications
- Current or history of thrombophlebitis or thromboembolic disorders
- Known or suspected carcinoma of the breast
- Known or suspected estrogen-dependent neoplasia
- Undiagnosed abnormal genital bleeding
- Current or history of cerebrovascular or coronary artery disease
- Liver tumors or active hepatic disease
- Known or suspected pregnancy
- Hypersensitivity to any component
Warnings and Precautions
Boxed Warning: Cigarette smoking increases risk of serious cardiovascular side effects. Women over 35 years who smoke should not use combination oral contraceptives.Additional precautions:
- Increased risk of venous thromboembolism and arterial thromboembolism
- Elevated blood pressure
- Increased risk of liver tumors and gallbladder disease
- Carbohydrate and lipid metabolic effects
- Headache including migraine
- Ectopic pregnancy and uterine fibroid enlargement
- Depression and mood changes
- Visual changes with contact lens wear
Drug Interactions
Strong CYP3A4 inducers: Rifampin, carbamazepine, phenytoin, St. John's wort - may decrease contraceptive efficacy Strong CYP3A4 inhibitors: Ketoconazole, itraconazole - may increase estrogen levels Antibiotics: Some broad-spectrum antibiotics may reduce enterohepatic recirculation Anticoagulants: Potential alteration of anticoagulant effect Antidiabetic agents: May require dosage adjustment HIV medications: Protease inhibitors and NNRTIs may affect contraceptive levelsAdverse Effects
Common (>10%): Nausea, headache, breast tenderness, irregular bleeding, weight changes, mood changes Serious (<1%):- Venous thromboembolism (DVT, PE)
- Arterial thromboembolism (MI, stroke)
- Hepatic adenomas
- Gallbladder disease
- Hypertension
- Pancreatitis
Monitoring Parameters
- Blood pressure at baseline and periodically
- BMI and weight
- Signs and symptoms of thromboembolism
- Liver function tests if clinically indicated
- Headache pattern and characteristics
- Mood changes and depressive symptoms
- Breakthrough bleeding patterns
- Annual well-woman examination including breast and pelvic exams
Patient Education
- Take tablet at same time daily for maximum effectiveness
- Use backup contraception during first 7 days of initial use
- Report severe abdominal pain, chest pain, headaches, eye problems, or leg pain immediately
- Notify healthcare providers of oral contraceptive use
- Understand that this product does not protect against HIV or other STIs
- Report missed periods or suspected pregnancy
- Smoking is contraindicated while taking this medication
- Be aware of potential drug interactions with other medications
References
1. Curtis KM, Tepper NK, Jatlaoui TC, et al. U.S. Medical Eligibility Criteria for Contraceptive Use, 2016. MMWR Recomm Rep. 2016;65(3):1-103. 2. Practice Bulletin No. 206: Use of Hormonal Contraception in Women with Coexisting Medical Conditions. Obstet Gynecol. 2019;133(2):e128-e150. 3. Junel® [package insert]. Pomona, NY: Duramed Pharmaceuticals; 2021. 4. Stegeman BH, de Bastos M, Rosendaal FR, et al. Different combined oral contraceptives and the risk of venous thrombosis: systematic review and network meta-analysis. BMJ. 2013;347:f5298. 5. Arowojolu AO, Gallo MF, Lopez LM, Grimes DA. Combined oral contraceptive pills for treatment of acne. Cochrane Database Syst Rev. 2012;(7):CD004425.