Introduction
Jencycla (norethindrone 0.35 mg) is a progestin-only oral contraceptive pill, commonly referred to as a "mini-pill." It is FDA-approved for pregnancy prevention and represents an important option for individuals who cannot or prefer not to use estrogen-containing contraceptives. Unlike combination oral contraceptives, Jencycla contains only a progestin component, making it suitable for specific patient populations with contraindications to estrogen.
Mechanism of Action
Norethindrone, the active ingredient in Jencycla, exerts its contraceptive effects through multiple mechanisms:
- Cervical mucus alteration: Thickens cervical mucus, creating a barrier that impedes sperm penetration
- Endometrial changes: Causes endometrial thinning, creating an unfavorable environment for implantation
- Ovulation suppression: Inhibits the midcycle luteinizing hormone (LH) surge in approximately 40-50% of cycles
- Tubal motility effects: Alters fallopian tube motility, affecting ovum transport
The contraceptive efficacy primarily relies on the first two mechanisms, as ovulation inhibition occurs inconsistently with progestin-only pills.
Indications
FDA-approved indications:- Prevention of pregnancy
- Menstrual cycle regulation
- Treatment of endometriosis-associated pain
- Management of abnormal uterine bleeding
- Luteal phase support in fertility treatments
Dosage and Administration
Standard dosing:- One tablet (0.35 mg norethindrone) taken orally at the same time each day
- Continuous dosing without hormone-free intervals
- Postpartum patients: May initiate immediately postpartum (non-breastfeeding) or after 4 weeks (breastfeeding)
- Post-abortion: May begin immediately following first-trimester abortion
- Renal impairment: No dosage adjustment required
- Hepatic impairment: Contraindicated in hepatic impairment
- Geriatric patients: Not indicated in postmenopausal women
- Adolescents: Safe and effective for pediatric patients who have reached menarche
- <3 hours late: Take missed pill immediately and resume regular schedule
- >3 hours late: Take missed pill immediately, use backup contraception for 48 hours, and resume regular schedule
Pharmacokinetics
Absorption:- Rapidly absorbed with peak plasma concentrations reached within 1-2 hours
- Absolute bioavailability approximately 77%
- Food does not significantly affect absorption
- Volume of distribution: Approximately 4 L/kg
- Protein binding: 61% bound to albumin, 36% bound to sex hormone-binding globulin (SHBG)
- Crosses placenta and is excreted in breast milk
- Extensive hepatic metabolism primarily via CYP3A4
- Metabolites include norethindrone sulfate, norethindrone glucuronide, and various hydroxylated metabolites
- Elimination half-life: 5-14 hours
- Excretion: Urine (33%), feces (45%)
- Clearance: Approximately 4-6 L/hour/kg
Contraindications
- Known or suspected pregnancy
- Current or history of breast cancer
- Undiagnosed abnormal genital bleeding
- Liver tumors (benign or malignant) or active liver disease
- Hypersensitivity to any component of Jencycla
- Acute arterial thromboembolic disease (current or history)
- Hepatic impairment
Warnings and Precautions
Ectopic pregnancy risk: Women with history of ectopic pregnancy, tubal surgery, or pelvic inflammatory disease have increased risk of ectopic pregnancy Ovarian cysts: Functional ovarian cysts may occur and usually resolve spontaneously Carbohydrate metabolism: May decrease glucose tolerance; monitor diabetic patients closely Depression: May exacerbate depression; monitor patients with history of depression Bleeding patterns: Irregular bleeding is common, especially during first few months of use Liver function: Discontinue if jaundice develops Vision changes: May cause corneal edema; discontinue if visual changes or contact lens intolerance occurs Surgical procedures: Discontinue at least 4 weeks before elective surgery associated with thromboembolism riskDrug Interactions
Strong CYP3A4 inducers:- Rifampin, carbamazepine, phenytoin, St. John's wort
- Effect: Decreased norethindrone concentrations → reduced efficacy
- Management: Use alternative contraception or backup method
- Ketoconazole, itraconazole, clarithromycin
- Effect: Increased norethindrone concentrations → potential increased adverse effects
- Management: Monitor for progestin-related side effects
- Penicillins, tetracyclines (theoretical concern)
- Effect: Possible reduced efficacy due to enterohepatic recirculation interruption
- Management: Use backup contraception during and for 7 days after antibiotic course
- Lamotrigine
- Effect: Decreased lamotrigine concentrations
- Management: Monitor lamotrigine levels and seizure control
Adverse Effects
Very common (>10%):- Irregular menstrual bleeding
- Amenorrhea
- Headache
- Breast tenderness
- Nausea
- Dizziness
- Fatigue
- Mood changes
- Acne
- Weight changes
- Decreased libido
- Ectopic pregnancy
- Ovarian cysts
- Thromboembolic events
- Hepatic adenomas
- Depression
- Allergic reactions
Monitoring Parameters
Prior to initiation:- Pregnancy test
- Blood pressure
- Medical history including contraindications
- Breast examination
- Liver function assessment
- Regular blood pressure monitoring
- Annual breast examination
- Symptom assessment for thromboembolism
- Menstrual pattern documentation
- Mood assessment
- Weight monitoring
- Glucose monitoring in diabetic patients
- 3-month follow-up for bleeding pattern assessment
- Annual comprehensive evaluation
Patient Education
Administration:- Take at the same time every day (time consistency is critical for efficacy)
- Use backup contraception for 48 hours if dose is >3 hours late
- Do not discontinue without healthcare provider consultation
- Typical use failure rate: 7-9%
- Perfect use failure rate: 0.5%
- Effectiveness decreases with inconsistent timing
- Expect irregular bleeding patterns, especially during first 3 months
- Report severe abdominal pain (possible ectopic pregnancy)
- Report chest pain, shortness of breath, severe headaches, or visual changes
- Report symptoms of depression or mood changes
- Does not protect against sexually transmitted infections
- May affect menstrual cycle regularity for several months after discontinuation
- Fertility typically returns rapidly after discontinuation
- Store at room temperature, protected from moisture
References
1. FDA Prescribing Information: Jencycla (norethindrone) tablets. 2013. 2. Curtis KM, Jatlaoui TC, Tepper NK, et al. U.S. Selected Practice Recommendations for Contraceptive Use, 2016. MMWR Recomm Rep. 2016;65(4):1-66. 3. Kaunitz AM. Progestin-only oral contraception: a comprehensive review. Contraception. 1994;50(6 Suppl 1):S1-S195. 4. Lopez LM, Grey TW, Stuebe AM, Chen M, Truitt ST, Gallo MF. Combined hormonal versus nonhormonal versus progestin-only contraception in lactation. Cochrane Database Syst Rev. 2015;(3):CD003988. 5. Shulman LP. The state of hormonal contraception today: established and emerging noncontraceptive health benefits. Am J Obstet Gynecol. 2011;205(4 Suppl):S4-S8. 6. Trussell J. Contraceptive failure in the United States. Contraception. 2011;83(5):397-404. 7. World Health Organization. Medical Eligibility Criteria for Contraceptive Use. 5th ed. Geneva: WHO; 2015. 8. Zieman M, Hatcher RA. Managing Contraception. 2016-2017 edition. Tiger, GA: Bridging the Gap Foundation; 2016.