Twirla

Twirla is an FDA-registered drug product whose active ingredient is LEVONORGESTREL/ETHINYL ESTRADIOL. It is labelled by Agile Therapeutics, Inc. taken by transdermal and marketed as a human prescription drug product. Identifiers on file: NDC 71671-100, application NDA204017, label effective 20260630. This page reproduces the FDA-approved label text so you can check what a product is, who makes it and how it is supplied before discussing it with a pharmacist or prescriber.

Across FDA labelling, products containing LEVONORGESTREL/ETHINYL ESTRADIOL are most often described in connection with: indicated method, women reproductive, combined hormonal, contraceptive appropriate, consider twirla, reduced effectiveness, specific populations, clinical studies. Wording differs between labels, and the full indications section on this page takes precedence when it is present.

1 INDICATIONS AND USAGE TWIRLA is indicated as a method of contraception for use in women of reproductive potential with a BMI < 30 kg/m 2 for whom a combined hormonal contraceptive is appropriate. Limitation of Use Consider TWIRLA’s reduced effectiveness in women with a BMI ≥ 25 to < 30 kg/m 2 before prescribing TWIRLA [see Use in Specific Populations ( 8.9 ) and Clinical Studies ( 14 )] . TWIRLA is contraindicated in women with a BMI ≥ 30 kg/m 2 [see Contraindications ( 4 )] . TWIRLA is a combination of levonorgestrel, a progestin, and ethinyl estradiol, an estrogen, indicated as a method of contraception for use in women of reproductive potential with a BMI < 30 kg/m 2 for whom a combined hormonal contraceptive is appropriate. ( 1 ) Limitation of Use Consider TWIRLA’s reduced effectiveness in women with a BMI ≥ 25 to < 30 kg/m 2 before prescribing. ( 4 , 8.9 , 14 )

2 DOSAGE AND ADMINISTRATION For transdermal use only ( 2.2 ) Apply one TWIRLA transdermal system (TDS) every week for three consecutive weeks ( 2.1 , 2.2 ) Apply TWIRLA to one of the following sites: abdomen, buttock or upper torso (excluding breasts) ( 2.2 ) Do not cut or alter the TDS in any way ( 2.2 ) 2.1 How to Start Using TWIRLA See the FDA-approved patient labeling ( Instructions for Use ) . The TWIRLA transdermal system (TDS) is used in a 28-day (four-week) cycle. A new TDS is applied and worn for seven days for three consecutive weeks (Weeks 1, 2, and 3). No TDS is worn during Week 4 (the TDS-Free Week), when withdrawal bleeding is expected. On the day after Week 4 ends, a new 28-day cycle is started by applying a new TDS. Under no circumstances should there be more than a 7-day TDS-free interval between dosing cycles. Breakthrough (Unscheduled) Bleeding or Spotting Occurrence If unscheduled (breakthrough) spotting or bleeding occurs, instruct the woman to continue the same regimen. If the bleeding is persistent or prolonged consider causes other than TWIRLA. If the bleeding is persistent or prolonged, instruct the woman to consult with her healthcare provider. In Case of Skin Irritation If TDS use results in uncomfortable irritation, the TDS may be removed, and a new TDS may be applied to a different location until the next “Patch Change Day”. Only one TDS should be worn at a time. Every new TDS should be applied on the same day of the week. This day is known as the “Patch Change Day.” For example, if the first TDS is applied on a Sunday, all subsequent TDS should be applied on a Sunday. There are multiple options for starting the TDS, and the woman should choose the option that is most appropriate (see Table 1): Table 1: Instructions for Administration Starting TWIRLA in women with no current use of hormonal contraception Day 1 Start The woman should apply the first TDS during the first 24 hours of menstruation. The woman should apply a new TDS each week for three weeks (21 total days). No TDS is worn during Week Four (the “Patch-Free Week”). If a TDS is applied after the first 24 hours of menstruation, non-hormonal back-up contraception (such as condoms and spermicide, or diaphragm and spermicide) is needed for the first 7 days of the first cycle only. Switching from another contraceptive method Oral combination hormonal contraception (oral CHC) Start TWIRLA: The woman should complete the current pill cycle and apply the first TWIRLA TDS on the day the next pill cycle would normally start. If menses does not occur within a week after taking the last active pill, instruct the woman to consult with a healthcare professional to be sure that pregnancy has not occurred. If no pregnancy has occurred, TWIRLA may be started for contraception. If TWIRLA is applied more than a week after taking the last active pill, non-hormonal back-up contraception (such as condoms and spermicide, or diaphragm and spermicide) should be used concurrently for the first 7 days of TDS use. Transdermal system The woman should complete the current TDS cycle and apply the first TWIRLA TDS on the day the next TDS cycle would normally start. If menses does not occur within a week after removing the last TDS, instruct the woman to consult with a healthcare professional to be sure that pregnancy has not occurred. If no pregnancy has occurred, TWIRLA may be started for contraception. If TWIRLA is applied more than a week after removal of the last TDS, non-hormonal back-up contraception (such as condoms and spermicide, or diaphragm and spermicide) should be used concurrently for the first 7 days of TDS use. Vaginal ring The woman should complete the current vaginal ring cycle and apply the first TWIRLA TDS on the day the next vaginal ring would normally be inserted. If menses does not occur within a week after removing the last vaginal ring, instruct the woman to consult with a healthcare professional to be sure that pregnancy has not occurred. If no pregnancy has occurred, TWIRLA may be started for contraception. If TWIRLA is applied more than a week after removal of the last vaginal ring, non-hormonal back-up contraception (such as condoms and spermicide, or diaphragm and spermicide) should be used concurrently for the first 7 days of TDS use. Injection The woman should apply the first TDS on the day the next injection would normally occur. Intrauterine system (IUS) The woman should apply the first TDS on the day of IUS removal. Implant The woman should apply the first TDS on the day of implant removal. Progestin-only pill The woman should apply the first TDS on the day the next progestin-only pill cycle would normally start. Use after an abortion or miscarriage: TWIRLA may be started immediately for contraception within the first 5 days following a complete first trimester abortion or miscarriage without additional back-up contraception. If more than 5 days have elapsed from the first trimester abortion or miscarriage, then the woman should be advised to use non-hormonal contraception (such as condoms and spermicide, or diaphragm and spermicide) and follow instructions for starting TWIRLA for the first time. Ovulation may occur within 10 days of an abortion or miscarriage. TWIRLA should not be started earlier than 4 weeks after a second trimester abortion or miscarriage due to the increased risk of thromboembolism [see Warnings and Precautions ( 5.1 )] . Use of TWIRLA after childbirth: For women who elect not to breastfeed, do not start TWIRLA sooner than 4 weeks after childbirth given the increased risk for thromboembolism [see Use in Specific Populations ( 8.2 )] . If a woman begins using TWIRLA postpartum and has not yet had a period, consider the possibility of ovulation and pregnancy. If the woman is not pregnant, instruct her to use non-hormonal back-up contraception (such as condoms and spermicide, or diaphragm and spermicide) for the first 7 days of TDS use [see Warnings and Precautions ( 5.1 ) and Use in Specific Populations ( 8.1 )] . 2.2 Important Application Instructions See the FDA-approved patient labeling ( Instructions for Use ) . TWIRLA TDS is applied once weekly for three weeks. Each TWIRLA TDS should be worn for one week. Instruct women to wear only one TWIRLA TDS at any time. To achieve maximum contraceptive effectiveness, TWIRLA must be used exactly as directed. The failure rate may increase when TDS application is delayed/missed or when TDS is applied incorrectly. Apply TWIRLA to clean, dry, and intact skin at the selected application site. Application sites include: the abdomen, buttock or upper torso (excluding the breasts). When applying a new TWIRLA TDS, do not apply the new TDS directly over the previous TDS site. Do not apply TWIRLA to skin that has been exposed to powder, oil, moisturizer, or lotion. Advise women not to routinely use large amounts of body lotions or oils at application sites. Prolonged exposure to water may interfere with adherence of TWIRLA. Do not cut or alter TWIRLA in any way, the whole TDS should be applied. If the TWIRLA TDS is cut or damaged or altered in size, contraceptive efficacy may be impaired. If the TWIRLA TDS lifts at the edges, reattach TWIRLA by pressing firmly and smoothing down the edges of the system. If TWIRLA comes off completely, reapply the TWIRLA TDS that detached. Discard TWIRLA by folding the used TDS so that the adhesive side sticks to itself and safely discard in the trash. MANAGING PARTIAL OR COMPLETE TDS DETACHMENTS (see Table 2 ) The TWIRLA TDS must adhere securely to the skin to work properly. Prolonged water exposure may compromise the TDS’s adherence. As a result, the woman should be instructed to check the TDS for partial or complete TDS detachment not only daily but also after prolonged water exposure. If the TDS becomes partially or completely detached and remains detached, insufficient drug delivery may occur. Partial TDS detachment should be resolved since it can lead to the TDS getting caught on clothing and detaching. The woman should not try to reapply a TDS if it is no longer sticky, if it has become stuck to itself or another surface, and/or if it has other material stuck to it. If a TDS edge lifts up: The woman should press down firmly on the TDS with the palm of the hand for 10 seconds, making sure that the whole TDS is adhered to her skin. Then run fingers over the entire surface area to smooth out any wrinkles around the edges of the TDS. If the lifted edge of the TDS does not stick completely after attempted re-adhesion, the TDS should be removed, and a new replacement TDS applied. Do not tape or wrap the TDS to the skin or reapply a TDS that is partially adhered to clothing. If the TDS has been off or partially off: For less than one day , the woman should try to reapply it. If the TDS does not adhere completely, apply a new TDS immediately. No back-up contraception is needed and the “Patch Change Day” will stay the same. For more than one day OR if unsure of the timeframe , the woman may not be protected from pregnancy. To reduce this risk, apply a new TDS and start a new 4-week cycle. The woman will now have a new “Patch Change Day” and MUST USE NON-HORMONAL BACK-UP CONTRACEPTION (such as condoms and spermicide, or diaphragm and spermicide) for the first 7 days of the new cycle. 2.3 Missed Doses Instruct women about the handling of missed doses (e.g., missed or delayed TDS application) and to follow the dosing instructions provided in the FDA-approved patient labeling. FORGETTING TO CHANGE THE TDS: At the start of any TDS cycle (Week 1/Day 1): THE WOMAN MAY NOT BE PROTECTED FROM PREGNANCY. The woman should apply the first TDS of her new cycle as soon as she remembers, and this becomes the new "Patch Change Day" and a new "Day 1" of the cycle. The woman should use non-hormonal back-up contraception (such as condoms and spermicide, or diaphragm and spermicide) for the first 7 days of the new cycle. In the middle of the TDS cycle (Week 2/Day 8 or Week 3/Day 15), for 1 or 2 days (up to 48 hours): The woman should apply a new TDS immediately. The next TDS should be applied on the usual "Patch Change Day". No back-up contraception is needed. For more than 2 days (48 hours or more): THE WOMAN MAY NOT BE PROTECTED FROM PREGNANCY. The woman should stop the current contraceptive cycle and start a new four-week cycle immediately by putting on a new TDS. This is now a new "Patch Change Day" and a new "Day 1" of the cycle. Non-hormonal back-up contraception must be used for 7 days. At the end of the TDS cycle Week 3 (Day 22): If the woman forgets to remove her TDS, she should take it off as soon as she remembers. The next cycle should be started on the usual "Patch Change Day", which is the day after Day 28. No back-up contraception is needed. Table 2: Managing Partial or Complete TDS Detachments and Late/Missed TDS Applications Scenario Results in New TDS-Change Day Starts New Cycle Back-up Contraception Required (7 Days) Did not apply TDS on scheduled Day 1/Week 1 of new cycle (late TDS-on day) Yes Yes Yes TDS detached for < 24 hours No No No TDS detached for ≥ 24 hours, or unsure duration Yes Yes Yes < 48 hours late for Patch Change Day (Day 8 or 15) No No No ≥ 48 hours late for Patch Change Day (Day 8 or 15) Yes Yes Yes Forgets to remove last TDS on Day 22 No No No Under no circumstances should there be more than a seven-day TDS-free interval between cycles. If there are more than 7 TDS-free days, THE WOMAN MAY NOT BE PROTECTED FROM PREGNANCY and non-hormonal back-up contraception (such as a condoms and spermicide, or diaphragm and spermicide) must be used for 7 days. As with CHCs, the risk of ovulation increases with each day beyond the recommended drug-free period. If the woman has intercourse during such an extended TDS-free interval, consider the possibility of pregnancy.

4 CONTRAINDICATIONS Twirla is contraindicated in females who are known to have or develop the following conditions: At high risk of arterial or venous thrombotic diseases. Examples include women who Smoke, if over age 35 [see Boxed Warning and Warnings and Precautions ( 5.1 )] Have current or history of deep vein thrombosis or pulmonary embolism [see Warnings and Precautions ( 5.1 )] Have cerebrovascular disease [see Warnings and Precautions ( 5.1 )] Have coronary artery disease [see Warnings and Precautions ( 5.1 )] Have thrombogenic valvular or thrombogenic rhythm diseases of the heart (for example, subacute bacterial endocarditis with valvular disease, or atrial fibrillation) [see Warnings and Precautions ( 5.1 )] Have inherited or acquired hypercoagulopathies [see Warnings and Precautions ( 5.1 )] Have uncontrolled hypertension or hypertension with vascular disease [see Warnings and Precautions ( 5.4 )] Have diabetes mellitus and are over age 35, diabetes mellitus with hypertension or vascular disease or other end-organ damage, or diabetes mellitus of > 20 years duration [see Warnings and Precautions ( 5.7 )] Have headaches with focal neurological symptoms, migraine headaches with aura Women over age 35 with any migraine headaches [see Warnings and Precautions ( 5.8 )] BMI ≥ 30 kg/m 2 . Compared to women with a lower BMI, women with a BMI ≥ 30 kg/m 2 had reduced effectiveness and may have a higher risk for VTEs [see Warnings and Precautions ( 5.1 ), Use in Specific Populations ( 8.9 ) and Clinical Studies ( 14 )]. Liver tumors (benign or malignant), acute viral hepatitis, or severe (decompensated) cirrhosis, or liver disease [see Warnings and Precautions ( 5.2 )] Undiagnosed abnormal uterine bleeding [see Warnings and Precautions ( 5.9 )] Pregnancy, given there is no reason to use CHCs during pregnancy [see Use in Specific Populations ( 8.1 )] Current diagnosis of, or history of, breast cancer, which may be hormone-sensitive [see Warnings and Precautions ( 5.11 )] Hypersensitivity to any components of TWIRLA. Observed reactions include itching and irritation at the TDS application site [see Adverse Reactions ( 6.1 )] Use of Hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, due to the potential for alanine aminotransferase (ALT) elevations [see Warnings and Precautions ( 5.3 )] High risk of arterial or venous thrombotic diseases ( 4 ) Breast cancer ( 4 ) BMI ≥ 30 kg/m 2 ( 4 ) Liver tumors, acute viral hepatitis or decompensated cirrhosis ( 4 ) Undiagnosed abnormal uterine bleeding ( 4 ) Pregnancy ( 4 , 8.1 ) Hypersensitivity reactions to components of TWIRLA ( 4 ) Use of Hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir ( 4 )

6 ADVERSE REACTIONS The following serious adverse reactions with the use of CHCs, including TWIRLA, are discussed elsewhere in the labeling: Thromboembolic Disorders and Other Vascular Conditions [see Warnings and Precautions ( 5.1 )] Liver disease [see Warnings and Precautions ( 5.3 )] The most common adverse reactions (≥ 2%) in clinical trials for TWIRLA are application site disorders, nausea, headache, dysmenorrhea, and increased weight. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Exeltis USA, Inc. at 1-877-324-9349 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of one product cannot be directly compared to rates in the clinical trials of another product and may not reflect the rates observed in practice. The safety of TWIRLA was evaluated in a 12-month, multicenter, open-label, single-arm clinical trial (NCT02158572) conducted in the United States [see Clinical Studies ( 14 )] . Women applied TWIRLA (40 mcg LNG/10 mcg EE) for 13 28-day treatment cycles. One treatment cycle is defined as three consecutive weeks that one TWIRLA TDS is applied for seven-day wear followed by one week that TWIRLA is not applied. The safety population for this clinical trial was composed of 2,031 women that contributed 18,841 treatment cycles of exposure. Of these 2,031 women, 989 women completed 13 treatment cycles. The mean age was 27.5 years. The mean BMI for the safety population was 28.3 kg/m 2 . The BMI of the safety population was widely distributed: 39.4% had a BMI < 25 kg/m 2 , 25.3% had a BMI ≥ 25 kg/m 2 and < 30 kg/m 2 , and 35.3% had a BMI ≥ 30 kg/m 2 . For women who received TWIRLA, the most common reasons for discontinuation from the study were a womans decision (15.3%) and lost to follow-up (11.3%). Discontinuation due to an adverse reaction occurred in 10.9% of women. The most common (≥ 2%) adverse reactions leading to discontinuation were application site disorder (3.1%) and any bleeding irregularities (2.2%). The most common adverse reactions that occurred in ≥ 2% of the 2,031 women that used TWIRLA are shown in Table 3. Table 3: Adverse Drug Reactions Reported by 2% of TWIRLA-Treated Women in One Phase 3 Clinical Trial Adverse reaction TWIRLA (n=2,031) General disorders and administration site conditions Application site disorder* 6.2% Gastrointestinal disorders Nausea 4.1% Nervous system disorders Headache 3.6% Reproductive system and breast disorder Dysmenorrhoea 2.3% Investigations Weight increased 2.0% *Represents a bundle of similar terms that include the following adverse reactions: application site acne, hemorrhage, pustules, dermatitis, hypersensitivity, rash, discoloration, induration, reaction, dryness, irritation, ulcer, erosion, pain, urticaria, erythema, papules, vesicles, exfoliation, pruritis. Venous Thromboembolic Events (VTEs) A total of four VTEs (including pulmonary embolism and deep vein thrombosis) in TWIRLA-treated patients were identified in the clinical trial. Of these, all were in women with a BMI > 30 kg/m 2 [see Contraindications ( 4 )] . Other Serious Adverse Reactions The following serious adverse reactions occurred in < 1% of women who received TWIRLA: cholelithiasis, cholecystitis, major depression, suicidal ideation, appendicitis, ectopic pregnancy, pneumonia, and gastroenteritis. 6.2 Postmarketing Experience Five studies that compared breast cancer risk between ever-users (current or past use) of combined oral contraceptives (COCs) and never-users of COCs reported no association between ever use of COCs and breast cancer risk, with effect estimates ranging from 0.90 - 1.12 (Figure 2). Three studies compared breast cancer risk between current or recent COC users (<6 months since last use) and never users of COCs (Figure 2). One of these studies reported no association between breast cancer risk and COC use. The other two studies found an increased relative risk of 1.19 - 1.33 with current or recent use. Both of these studies found an increased risk of breast cancer with current use of longer duration, with relative risks ranging from 1.03 with less than one year of COC use to approximately 1.4 with more than 8-10 years of COC use. Figure 2. Relevant Studies of Risk of Breast Cancer with Combined Oral Contraceptives RR = relative risk; OR = odds ratio; HR = hazard ratio. “ever COC” are females with current or past COC use; “never COC use” are females that never used COCs. image description

What is Twirla used for?
1 INDICATIONS AND USAGE TWIRLA is indicated as a method of contraception for use in women of reproductive potential with a BMI < 30 kg/m 2 for whom a combined hormonal contraceptive is appropriate. Limitation of Use Consider TWIRLA’s reduced effectiveness in women with a BMI ≥ 25 to < 30 kg/m 2 before prescribing TWIRLA [see Use in Specific Populations ( 8.9 ) and Clinical Studies ( 14 )] . …

Who makes Twirla?
Agile Therapeutics, Inc. is the labeler of record for Twirla.

What form does Twirla come in?
administered by transdermal. Strengths and pack sizes vary by label, so compare the NDC on your pack with the identifier listed on this page.

Is Twirla prescription or over-the-counter?
The FDA label for this product is recorded as human prescription drug. Marketing status can differ between strengths and countries, so check the dispensing rules where you live.

Has Twirla been recalled?
No FDA recall record in our database matches this product name or manufacturer. Recall data is updated periodically, so a very recent notice may not appear here yet.

Where does this information come from?
All content is reproduced from FDA Structured Product Labelling data via openFDA. It is provided for identification and reference only and is not medical advice.