Jolessa - Drug Monograph

Introduction

Jolessa is an extended-cycle oral contraceptive containing a combination of ethinyl estradiol and levonorgestrel. It is formulated to provide 91 days of continuous hormone administration followed by a 7-day hormone-free interval, resulting in four menstrual periods per year rather than the traditional monthly cycles.

Mechanism of Action

Jolessa works through multiple mechanisms to prevent pregnancy. The primary actions include:

• Suppression of gonadotropins (FSH and LH) via negative feedback on the hypothalamus and pituitary
• Inhibition of ovulation through prevention of the LH surge
• Thickening of cervical mucus, creating a barrier to sperm penetration
• Alteration of endometrial lining, making it less receptive to implantation

The combination of ethinyl estradiol (estrogen component) and levonorgestrel (progestin component) provides synergistic contraceptive effects.

Indications

• Prevention of pregnancy
• Management of heavy menstrual bleeding (when used for contraception)
• Treatment of dysmenorrhea (when used for contraception)

Dosage and Administration

• Tablets should be taken at approximately the same time each day
• Initiation: Start on first day of menstrual period or first Sunday after menstrual period begins
• Missed dose protocol:

- 1-2 tablets missed: Take missed tablet as soon as remembered and continue regular schedule - ≥3 tablets missed: Use backup contraception for 7 days and consult healthcare provider

• Hepatic impairment: Contraindicated in acute or chronic liver disease
• Renal impairment: No dosage adjustment required
• Geriatric patients: Not indicated in postmenopausal women
• Adolescents: May be used after menarche

Pharmacokinetics

• Ethinyl estradiol: Rapidly and completely absorbed, peak concentration in 1-2 hours
• Levonorgestrel: Completely absorbed, peak concentration in 1-2 hours
• Bioavailability: Ethinyl estradiol ~40%, Levonorgestrel ~100%

• Ethinyl estradiol: Volume of distribution ~20 L/kg, highly bound to albumin
• Levonorgestrel: Volume of distribution ~1.8 L/kg, bound to SHBG and albumin

• Hepatic metabolism via cytochrome P450 system (primarily CYP3A4)
• Extensive first-pass metabolism
• Ethinyl estradiol undergoes enterolepatic circulation

• Ethinyl estradiol: Half-life ~24 hours, excreted in urine and feces
• Levonorgestrel: Half-life ~30 hours, excreted in urine and feces

Contraindications

• Current or history of thrombophlebitis or thromboembolic disorders
• Current or history of cerebrovascular or coronary artery disease
• Known or suspected carcinoma of the breast
• Known or suspected estrogen-dependent neoplasia
• Undiagnosed abnormal genital bleeding
• Current or history of benign or malignant liver tumors
• Known or suspected pregnancy
• Hypersensitivity to any component of Jolessa
• Heavy smoking (≥15 cigarettes/day) in women over 35 years

Warnings and Precautions

• Increased risk of venous thromboembolism and arterial thromboembolism
• Elevated blood pressure requiring monitoring
• Increased risk of liver tumors (benign and malignant)
• Possible slight increase in frequency of breast cancer diagnosis
• Increased risk of gallbladder disease
• Carbohydrate and lipid metabolic effects
• Headache including migraine (new, recurrent, or worsening)
• Bleeding irregularities including unscheduled bleeding
• Ectopic pregnancy risk if pregnancy occurs while taking Jolessa

Drug Interactions

• Enzyme inducers: Carbamazepine, phenytoin, rifampin, St. John's wort (decreased efficacy)
• Antibiotics: Broad-spectrum antibiotics may decrease efficacy
• HIV medications: Protease inhibitors and NNRTIs may affect levels
• Anticoagulants: May decrease anticoagulant effect
• Cyclosporine: Increased levels requiring monitoring
• Lamotrigine: Decreased lamotrigine levels
• Thyroid hormones: May affect thyroid hormone requirements

Adverse Effects

• Headache
• Nausea
• Breast tenderness
• Unscheduled bleeding/spotting
• Weight changes
• Mood changes

• Venous thromboembolism
• Myocardial infarction
• Stroke
• Hypertension
• Gallbladder disease
• Hepatic adenomas
• Visual changes

Monitoring Parameters

• Blood pressure
• BMI
• Personal and family medical history
• Lipid profile (if indicated)
• Liver function tests (if indicated)

• Blood pressure every 6-12 months
• Annual comprehensive history and physical examination
• Symptom assessment for thromboembolic events
• Assessment of bleeding patterns
• Evaluation of side effects and tolerability
• Patient adherence assessment

Patient Education

• Take tablet at same time daily to maintain effectiveness
• Use backup contraception during first 7 days of initial cycle
• Report severe abdominal pain, chest pain, headaches, eye problems, or leg pain immediately
• Understand expected bleeding pattern changes (fewer periods per year)
• Recognize signs of pregnancy if suspected
• Inform healthcare providers about Jolessa use before any medical procedures
• Do not smoke while taking this medication
• Store at room temperature, protect from light and moisture
• Missed dose instructions: Follow package insert guidelines carefully
• Report any new medical conditions or medications to healthcare provider

References

1. FDA Prescribing Information: Jolessa (levonorgestrel/ethinyl estradiol) tablets. 2022. 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. Teal S, Edelman A. Contraception Selection, Effectiveness, and Adverse Effects: A Review. JAMA. 2021;326(24):2507-2518. 4. Practice Bulletin No. 206: Use of Hormonal Contraception in Women with Coexisting Medical Conditions. Obstet Gynecol. 2019;133(3):e128-e150. 5. 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. 6. World Health Organization. Medical Eligibility Criteria for Contraceptive Use. 5th edition. Geneva: WHO; 2015.