Introduction
Jolivette (norethindrone) is a progestin-only oral contraceptive pill, commonly referred to as a "mini-pill." It contains 0.35 mg of norethindrone as the active ingredient and is primarily used for pregnancy prevention. Unlike combination oral contraceptives, Jolivette does not contain estrogen, making it suitable for certain patient populations who cannot tolerate estrogen-containing products.
Mechanism of Action
Norethindrone, a synthetic progestin, exerts its contraceptive effects through multiple mechanisms:
- Thickening cervical mucus, creating a barrier to sperm penetration
- Suppressing ovulation in approximately 40-50% of cycles by inhibiting the midcycle surge of luteinizing hormone
- Creating endometrial changes that are unfavorable for implantation
The contraceptive efficacy primarily relies on consistent cervical mucus changes rather than consistent ovulation suppression.
Indications
- Prevention of pregnancy
- Off-label uses may include treatment of endometriosis-associated pain and abnormal uterine bleeding, though these are not FDA-approved indications for this specific formulation
Dosage and Administration
Standard dosing: One tablet (0.35 mg) taken orally at the same time every day, with no hormone-free interval Special populations:- Renal impairment: Use with caution; limited data available
- Hepatic impairment: Contraindicated in hepatic disease
- Geriatric patients: Not applicable (postmenopausal)
- Adolescents: May be used in reproductive-age adolescents
- <3 hours late: Take missed pill immediately and continue regular schedule
- >3 hours late: Take missed pill immediately, use backup contraception for 48 hours
Pharmacokinetics
Absorption: Rapidly absorbed with peak plasma concentrations occurring within 1-2 hours Distribution: Bound to sex hormone-binding globulin and albumin Metabolism: Extensive hepatic metabolism via reduction and conjugation Elimination: Half-life approximately 8 hours; excreted primarily in urine (50%) and feces (35%)Contraindications
- Current or history of breast cancer
- Hepatic tumors or active liver disease
- Undiagnosed abnormal genital bleeding
- Hypersensitivity to norethindrone or any component
- Current thrombophlebitis or thromboembolic disorders
Warnings and Precautions
- Ectopic pregnancy risk: Higher incidence compared to combination OCs; maintain high index of suspicion
- Ovarian cysts: May occur and usually resolve spontaneously
- Carbohydrate metabolism: May decrease glucose tolerance
- Lipid effects: May alter lipid profiles
- Vision changes: May cause corneal curvature changes
- Depression: May exacerbate pre-existing depression
Drug Interactions
Enzyme inducers: Carbamazepine, phenytoin, rifampin, St. John's wort (may decrease efficacy) Antibiotics: Limited evidence for interaction, but theoretical concern with broad-spectrum antibiotics HIV medications: Protease inhibitors and NNRTIs may alter levels Antifungals: Ketoconazole may increase norethindrone levelsAdverse Effects
Common (>10%):- Menstrual irregularities (spotting, amenorrhea, irregular bleeding)
- Headache
- Nausea
- Breast tenderness
- Weight changes
- Ectopic pregnancy
- Thrombotic events (lower risk than combination OCs)
- Hepatic adenomas
- Depression
- Allergic reactions
Monitoring Parameters
- Blood pressure at baseline and periodically
- Signs and symptoms of thromboembolism
- Menstrual pattern changes
- Mood changes
- Weight changes
- Liver function tests if clinically indicated
- Pregnancy testing if suspected
Patient Education
- Take at the same time daily for maximum efficacy
- Use backup contraception if >3 hours late taking pill
- Expect menstrual pattern changes, especially during first 3-6 months
- Report severe abdominal pain (possible ectopic pregnancy)
- Notify healthcare providers of Jolivette use
- Does not protect against HIV or other STIs
- Effectiveness may be reduced with vomiting or diarrhea
- Return for annual contraceptive review
References
1. Curtis MG, Teal SB. Progestin-only contraceptives. In: Hatcher RA, et al. Contraceptive Technology. 21st ed. 2018. 2. FDA Prescribing Information: Jolivette (norethindrone) tablets. 2021. 3. Shulman LP. The state of the art in oral progestin-only contraception. Eur J Contracept Reprod Health Care. 2019;24(2):85-94. 4. Lopez LM, Grey TW, Stuebe AM, et al. Combined hormonal versus nonhormonal versus progestin-only contraception in lactation. Cochrane Database Syst Rev. 2015;(3):CD003988. 5. Practice Bulletin No. 152: Emergency contraception. Obstet Gynecol. 2015;126(3):e1-e11.