Twirla - Drug Monograph

Introduction

Twirla (levonorgestrel/ethinyl estradiol transdermal system) is a combination hormonal contraceptive patch containing both a progestin (levonorgestrel) and an estrogen (ethinyl estradiol). It is a weekly transdermal contraceptive system that provides an alternative to oral contraceptive pills for women seeking reversible pregnancy prevention.

Mechanism of Action

Twirla works through multiple mechanisms to prevent pregnancy. The combination of levonorgestrel and ethinyl estradiol:

• Inhibits ovulation by suppressing gonadotropin secretion
• Thickens cervical mucus, creating a barrier to sperm penetration
• Alters the endometrial lining, reducing the likelihood of implantation

The transdermal delivery system provides continuous hormone delivery through the skin into the systemic circulation.

Indications

Twirla is indicated for:

• Prevention of pregnancy in women with a body mass index (BMI) <30 kg/m²
• Use as a combined hormonal contraceptive

Dosage and Administration

• One patch applied weekly for 3 consecutive weeks
• Followed by 1 patch-free week
• Each patch delivers approximately 120 mcg of levonorgestrel and 30 mcg of ethinyl estradiol daily

• Apply to clean, dry, intact skin on the abdomen, buttocks, or upper torso (excluding breasts)
• Rotate application sites to minimize skin irritation
• Do not apply to irritated skin or areas where makeup, lotions, or powders are applied

• Not recommended for women with BMI ≥30 kg/m² due to increased risk of contraceptive failure
• Hepatic impairment: Contraindicated in women with acute or chronic liver disease
• Renal impairment: No dosage adjustment required

Pharmacokinetics

• Steady-state concentrations achieved within 2 days of application
• Bioavailability: Levonorgestrel ~85%, Ethinyl estradiol ~95%

• Levonorgestrel: Highly bound to SHBG and albumin
• Ethinyl estradiol: Approximately 98% bound to albumin

• Hepatic metabolism via cytochrome P450 system (primarily CYP3A4)
• Levonorgestrel: Extensive metabolism
• Ethinyl estradiol: Extensive first-pass metabolism

• Levonorgestrel: Terminal half-life ~20-32 hours
• Ethinyl estradiol: Terminal half-life ~10-20 hours
• Excretion: Primarily urinary and fecal

Contraindications

• Current or history of thrombophlebitis or thromboembolic disorders
• Known or suspected pregnancy
• Breast cancer or other estrogen-dependent neoplasia
• Undiagnosed abnormal genital bleeding
• Hepatic tumors or active liver disease
• Hypersensitivity to any component of Twirla
• BMI ≥30 kg/m²
• Smoking in women over 35 years old

Warnings and Precautions

• Cigarette smoking increases the risk of serious cardiovascular side effects
• Women over 35 years old who smoke should not use combined hormonal contraceptives

• Increased risk of venous thromboembolism (VTE)
• Cardiovascular risks including myocardial infarction and stroke
• Hypertension development or exacerbation
• Gallbladder disease
• Adverse lipid effects
• Carbohydrate metabolism effects
• Headache including migraine
• Ectopic pregnancy risk
• Liver disease and tumors
• Breast cancer risk
• Application site reactions

Drug Interactions

• Carbamazepine, phenytoin, rifampin, St. John's wort: May decrease contraceptive effectiveness

• Ketoconazole, itraconazole: May increase hormone levels

• Ascorbic acid and acetaminophen: May increase ethinyl estradiol levels
• Antibiotics: Potential decreased contraceptive effectiveness (controversial)
• HIV/HCV protease inhibitors: Variable effects on hormone levels

Adverse Effects

• Application site reactions (20%)
• Nausea (6%)
• Headache (6%)
• Breast tenderness (4%)
• Dysmenorrhea (3%)
• Abdominal pain (2%)
• Increased weight (2%)

• Venous thromboembolism
• Arterial thromboembolism
• Hypertension
• Hepatic adenomas
• Gallbladder disease
• Mood changes and depression

Monitoring Parameters

• Blood pressure
• BMI calculation
• Smoking status assessment
• Personal and family history of thromboembolism
• Lipid profile (if indicated)
• Liver function tests (if indicated)

• Blood pressure at least annually
• Regular BMI assessment
• Symptom assessment for thromboembolism
• Evaluation of persistent application site reactions
• Assessment of new headaches or migraine patterns
• Breast examination

• Signs and symptoms of thromboembolism (leg pain, chest pain, shortness of breath)
• Importance of regular patch change schedule
• Proper application and removal techniques
• Backup contraception requirement during first week of use
• Management of missed patches
• Signs of pregnancy to report
• Importance of reporting persistent headaches or visual changes

Patient Education

• Apply patch to clean, dry, intact skin on approved sites
• Change patch on the same day each week
• Use backup contraception during first 7 days of initial use
• If patch detaches, reapply or replace if necessary
• Do not apply makeup, lotions, or powders to application site
• Report any application site reactions that persist beyond a few days
• Immediately report signs of blood clots: leg pain, chest pain, shortness of breath, vision changes
• Inform healthcare providers about Twirla use before any medical procedures
• Understand that Twirla does not protect against HIV or other sexually transmitted infections

• Less than 48 hours late: Apply new patch immediately, no backup needed
• More than 48 hours late: Apply new patch, use backup contraception for 7 days
• May need to start new cycle depending on timing in cycle

References

1. FDA Prescribing Information: Twirla (levonorgestrel/ethinyl estradiol) transdermal system. 2020. 2. Archer DF, et al. Contraceptive efficacy and safety of a transdermal patch and an oral contraceptive: a randomized controlled trial. Obstet Gynecol. 2012;119(3):513-521. 3. Practice Bulletin No. 206: Use of Hormonal Contraception in Women with Coexisting Medical Conditions. Obstet Gynecol. 2019;133(2):e128-e150. 4. Curtis KM, et al. U.S. Medical Eligibility Criteria for Contraceptive Use, 2016. MMWR Recomm Rep. 2016;65(3):1-103. 5. Teal J, et al. Transdermal hormone delivery systems for contraception: a review of current status and future prospects. Expert Opin Drug Deliv. 2020;17(7):965-975.