INTROVALE Levonorgestrel and Ethinyl Estradiol tablets Kit, 3 pouches
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Estrogen class.
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🏭 Manufacturer & labeler
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🩺 Clinical
Oral contraceptives (birth-control pills) containing ethinyl estradiol (an estrogen) and levonorgestrel (a progestin) are used to prevent pregnancy. Estrogen and progestin are two female sex hormones. Combinations of estrogen and progestin work by preventing ovulation (the release of eggs from the ovaries). Oral contraceptives are an effective method of birth control, but they do not prevent the spread of human immunodeficiency virus (HIV, the virus that causes acquired immunodeficiency syndrome [AIDS]) and other sexually transmitted diseases.
Read the full MedlinePlus article ↗- It prevents pregnancy mainly by stopping your ovaries from releasing an egg. It also thickens the cervical mucus so sperm can't easily get through, and changes the uterine lining a...
- What exactly does this medication do, and how well does it work?
- The most common ones in the first few months are headaches, nausea, irregular bleeding or spotting, breast tenderness, and mood changes. Most of these tend to settle down after you...
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🧪 Inactive Ingredients / Excipients
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💲 Pricing
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| Price system | Per ea | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | $0.221 | $0.66 / 3 kit |
| Medicaid paysCMS SDUD · 12 mo | $0.3985 | $1.20 / 3 kit |
| Medicare drug plans payPart D · Q2 2026 | $0.4480 | $1.34 / 3 kit |
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Introvalethis 70700-0208-88 | Xiromed | 3 pouches | $0.221 | AB | Availability likely | — |
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⏳ Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
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🗺️ Medicaid utilization & spend
📊 Medicare Part D spend CMS · PART D · 2026 (Q1)
🔬 Reported adverse events (FAERS)
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📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 70700-0208-88 You're viewing this | 3 POUCH in 1 CARTON (70700-208-88) / 1 BLISTER PACK in 1 POUCH (70700-208-87) / 1 KIT in 1 BLISTER PACK | 2025-01-29 | Active |
🧭 About this NDC listing & data coverage
Kit / multi-component package
This NDC identifies a kit — a package containing more than one component. Structured data (pricing, ingredients, equivalents) is often reported per component rather than for the kit NDC itself, which can make this page look thinner than the components' own pages.
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| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | ✓ Available |
| Inactive ingredients (structured) | — Not published for this NDC The labeler did not submit a structured excipient list, or no SPL is available. |
| NADAC pharmacy acquisition price (CMS) | ✓ Available |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | — Not published for this NDC Most self-administered / retail products have no J-code — that is normal. |
| Medicaid utilization (CMS SDUD) | ✓ Available |
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📄 Full prescribing information FDA SPL
🚨 Boxed Warning ▾
WARNING: CIGARETTE SMOKING AND SERIOUS CARDIOVASCULAR EVENTS Cigarette smoking increases the risk of serious cardiovascular events from combination oral contraceptive (COC) use. This risk increases with age, particularly in women over 35 years of age, and with the number of cigarettes smoked. For this reason, COCs, including Introvale, are contraindicated in women who are over 35 years of age and smoke [see Contraindications (4) and Warnings and Precautions (5.1) ].
WARNING: CIGARETTE SMOKING AND SERIOUS CARDIOVASCULAR EVENTS See full prescribing information for complete boxed warning. Introvale is contraindicated in women over 35 years old who smoke. ( 4 ) Cigarette smoking increases the risk of serious cardiovascular events from combination oral contraceptive (COC) use.
( 5.1 )
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE Introvale is indicated for use by females of reproductive potential to prevent pregnancy. Introvale is a combination of levonorgestrel, a progestin, and ethinyl estradiol, an estrogen, indicated for use by females of reproductive potential to prevent pregnancy. ( 1 )
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION Take one tablet daily by mouth at the same time every day for 91 days. ( 2.1 ) Take tablets in the order directed on the Extended-Cycle Blister Pack. ( 2.2 )
2.1How to Start and Take Introvale Introvale is dispensed in an Extended-Cycle Blister Pack [ see How Supplied/Storage and Handling (16) ]. Introvale should be started on a Sunday (see Table 1). For the first cycle of a Sunday Start regimen, an additional method of contraception should be used until after the first 7 consecutive days of administration.
Table 1: Instructions for Administration of Introvale Starting Introvale in females with no current use of hormonal contraception (Sunday Start) Important: Consider the possibility of ovulation and conception prior to initiation of this product. Tablet Color: Introvale active tablets are white to off-white (Day 1 to Day 84). Introvale inactive tablets are green (Day 85 to Day 91).
Sunday Start: For each 91-day course, take in the following order: Take the first white to off-white tablet (0.15 mg of levonorgestrel and 0.03 mg ethinyl estradiol) on the first Sunday after the onset of menstruation. If menstruation begins on a Sunday, take the tablet on that day. Due to the potential risk of becoming pregnant, use additional non-hormonal contraception (such as condoms or spermicide) for the first 7 days of treatment.
Take subsequent white to off-white tablets once daily at the same time each day for a total of 84 days. Take one green tablet (inert) daily for the following 7 days and at the same time of day that active tablets were taken. A scheduled period should occur during the 7 days that the green tablets are taken.
Begin the next and all subsequent 91-day courses of Introvale without interruption on the same day of the week (Sunday) on which the patient began her first dose. Follow the same schedule as the initial 91-day course: a white to off-white tablet once a day for 84 days, and a green tablet once a day for 7 days. If the patient does not immediately start her next pill pack, instruct her to protect herself from pregnancy by using a non-hormonal back-up method of contraception until she has taken a white to off-white tablet daily for 7 consecutive days.
Switching from another contraceptive method to Introvale Start Introvale: Another oral contraceptive On the day when the new pack of the previous COC would have been started Transdermal patch On the day when the next application would have been scheduled. Vaginal ring On the day when the next insertion would have been scheduled. Injection On the day when the next injection would have been scheduled.
Intrauterine contraceptive (IUD) On the day of removal. If the IUD is not removed on first day of the patient’s menstrual cycle, additional non-hormonal contraception (such as condoms or spermicide) is needed for the first seven days of the first 91-day course. Implant On the day of removal.
Starting Introvale after Abortion or Miscarriage First-trimester After a first-trimester abortion or miscarriage, Introvale may be started immediately. An additional method of contraception is not needed if Introvale is started immediately. If Introvale is not started within 5 days after termination of the pregnancy, the patient should use additional non-hormonal contraception (such as condoms or spermicide) for the first seven days of her first 91-day course of Introvale.
Second-trimester Do not start Introvale until 4 weeks after a second-trimester abortion or miscarriage, due to the increased risk of thromboembolic disease. Start Introvale following the instructions in Table 1 for Sunday start. Use additional non-hormonal contraception (such as condoms or spermicide) for the first seven days of the patient’s first 91-day course of Introvale [see Contraindications (4) , Warnings and Precautions (5.1) ].
Starting Introvale after Childbirth Do not start Introvale until 4 weeks after delivery, due to the increased risk of thromboembolic disease. Start contra…
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Introvale is available as round, biconvex, unscored tablets, packaged in a carton of 3 pouches, each pouch contains Extended-Cycle Tablet Blister Pack of 91 tablets, each containing a 13-week supply of tablets in the following order: 84 white to off-white tablets, each containing 0.15 mg of levonorgestrel and 0.03 mg ethinyl estradiol; debossed with 212 on the one side and plain on the other side 7 green inert tablets debossed with 279 on the one side and plain on the other side. Introvale consists of 84 round, white to off-white tablets containing 0.15 mg of levonorgestrel and 0.03 mg of ethinyl estradiol, and 7 round, green inert tablets.
( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS Introvale is contraindicated in females who are known to have or develop the following conditions: A high risk of arterial or venous thrombotic diseases. Examples include females who are known to: 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 of 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, or over age 35 with any migraine headaches [see Warnings and Precautions (5.8) ] . Current diagnosis of, or history of breast cancer, which may be hormone sensitive [see Warnings and Precautions (5.11) ]. Liver tumors, acute viral hepatitis, or severe (decompensated) cirrhosis [see Warnings and Precautions (5.2) and Use in Specific Populations (8.6) ] .
Undiagnosed abnormal uterine bleeding [see Warnings and Precautions (5.9) ] . Use of Hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, due to the potential for ALT elevations [see Warnings and Precautions (5.3) ] . A high risk of arterial or venous thrombotic diseases ( 4 ) Liver tumors or liver disease, acute viral hepatitis or decompensated cirrhosis ( 4 ) Undiagnosed abnormal uterine bleeding ( 4 ) Breast cancer ( 4 ) Co-administration with Hepatitis C drug combinations containing ombitasvir/paritaprevir/ ritonavir, with or without dasabuvir.
( 4 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS Vascular risks: Stop if a thrombotic or thromboembolic event occurs. Stop at least 4 weeks before and through 2 weeks after major surgery. Start no earlier than 4 weeks after delivery, in women who are not breastfeeding.
Consider cardiovascular risk factors before initiating in all females, particularly those over 35 years. ( 5.1 , 5.5 ) Liver disease: Discontinue if jaundice occurs. ( 5.2 ) Hypertension: If used in women with well-controlled hypertension, monitor blood pressure and stop if blood pressure rises significantly.
( 5.4 ) Gallbladder disease: May cause or worsen gallbladder disease. ( 5.5 ) Adverse carbohydrate and lipid effects: Monitor glucose in prediabetic and diabetic women taking levonorgestrel and ethinyl estradiol tablets. Consider an alternate contraceptive method for women with uncontrolled dyslipidemia.
( 5.7 ) Headache: Evaluate significant change in headaches and discontinue if indicated. ( 5.8 ) Uterine bleeding: May cause irregular bleeding or amenorrhea. Evaluate for other causes if symptoms persist.
( 5.9 )
5.1Thromboembolic Disorders and Other Vascular Conditions Stop levonorgestrel and ethinyl estradiol tablets if an arterial or venous thrombotic/thromboembolic event occurs. Stop levonorgestrel and ethinyl estradiol tablets if there is unexplained loss of vision, proptosis, diplopia, papilledema, or retinal vascular lesions. Evaluate for retinal vein thrombosis immediately.
Discontinue levonorgestrel and ethinyl estradiol tablets during prolonged immobilization. If feasible, stop levonorgestrel and ethinyl estradiol tablets at least 4 weeks before and through 2 weeks after major surgery or other surgeries known to have an elevated risk of thromboembolism. Start levonorgestrel and ethinyl estradiol tablets no earlier than 4 weeks after delivery in females who are not breastfeeding.
The risk of postpartum thromboembolism decreases after the third postpartum week, whereas the likelihood of ovulation increases after the third postpartum week. Before starting levonorgestrel and ethinyl estradiol tablets evaluate any past medical history or family history of thrombotic or thromboembolic disorders and consider whether the history suggests an inherited or acquired hypercoagulopathy. Levonorgestrel and ethinyl estradiol tablets are contraindicated in females with a high risk of arterial or venous thrombotic/thromboembolic diseases [see Contraindications (4) ] .
Arterial Events COCs increase the risk of cardiovascular events and cerebrovascular events, such as myocardial infarction and stroke. The risk is greater among older women (>35 years of age), smokers, and females with hypertension, dyslipidemia, diabetes, or obesity. Levonorgestrel and ethinyl estradiol tablets are contraindicated in women over 35 years of age who smoke [see Contraindications (4) ] .
Cigarette smoking increases the risk of serious cardiovascular events from COC use. This risk increases with age, particularly in women over 35 years of age, and with the number of cigarettes smoked. Venous Events Use of COCs increases the risk of venous thromboembolic events (VTEs), such as deep vein thrombosis and pulmonary embolism.
Risk factors for VTEs include smoking, obesity, and family history of VTE, in addition to other factors that contraindicate use of COCs [see Contraindications (4) ] . While the increased risk of VTE associated with use of COCs is well-established, the rates of VTE are even greater during pregnancy, and especially during the postpartum period (see Figure 1). The rate of VTE in females using COCs has been estimated to be 3 to 9 cases per 10,000 woman years.
The risk of VTE is highest during the first year of use of a COC and when restarting hormonal contraception after a break of four weeks or longer. The risk of thromboembolic disease due to COCs gradually disappears after COC use is discontinued. Figure 1 shows the risk of developing a VTE for females who are not pregnant and do not use oral c…
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The following serious adverse reactions with the use of COCs are discussed elsewhere in the labeling: Serious cardiovascular events and stroke [see Boxed Warning and Warnings and Precautions (5.1) ] Vascular events [see Warnings and Precautions (5.1) ] Liver disease [see Warnings and Precautions (5.2) ] The most common adverse reactions (≥2%) reported during clinical trials were headache, menorrhagia, nausea, dysmenorrhea, acne, migraine, breast tenderness, weight increased, and depression. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Xiromed, LLC at 844-XIROMED (844-947-6633) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to the rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. The clinical trial that evaluated the safety and efficacy of levonorgestrel and ethinyl estradiol tablets was a 12-month, randomized, multicenter, open-label study, which enrolled women aged 18 to 40, of whom 456 took at least one dose of levonorgestrel and ethinyl estradiol tablets (345.14 woman-years of exposure) [see Clinical Studies (14) ] .
Adverse Reactions Leading to Study Discontinuation: 14.9% of the women discontinued from the clinical trial due to an adverse reaction; the most common adverse reactions (≥ 1% of women) leading to discontinuation in the levonorgestrel and ethinyl estradiol tablets group were menorrhagia (5.7%), mood swings (1.9%), weight/appetite increase (1.5%), and acne (1.3%). Common Adverse Reactions (≥ 2% of women): headache (20.6%), menorrhagia (11.6%), nausea (7.5%), dysmenorrhea (5.7%), acne (4.6%), migraine (4.4%), breast tenderness (3.5%), weight increased (3.1%), and depression (2.1%).
Serious Adverse Reactions: pulmonary embolus, cholecystitis.
6.2Postmarketing Experience Five studies that compared breast cancer risk between ever-users (current or past use) of 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.
The following adverse reactions have been identified during post-approval use of levonorgestrel and ethinyl estradiol tablets. Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Gastrointestinal disorders : abdominal distension, vomiting General disorders and administration site conditions : chest pain, fatigue, malaise, edema peripheral, pain Immune system disorder: hypersensitivity reactions, including itching, rash, and angioedema Investigations: blood pressure increased Musculoskeletal and connective tissue disorders : muscle spasms, pain in extremity Nervous system disorders : dizziness, loss of consciousness Psychiatric disorders : insomnia Reproductive and breast disorders : dysmenorrhea Skin and subcutaneous tissue disorders : alopecia Vascular disorders : thrombosis, pulmonary embolism, p…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS The sections below provide information on substances for which data on drug interactions with COCs are available. There is little information available about the clinical effect of most drug interactions that may affect COCs. However, based on the known pharmacokinetic effects of these drugs, clinical strategies to minimize any potential adverse effect on contraceptive effectiveness or safety are suggested.
Consult the approved product labeling of all concurrently used drugs to obtain further information about interactions with COCs or the potential for metabolic enzyme or transporter system alterations. No drug-drug interaction studies were conducted with levonorgestrel and ethinyl estradiol tablets. Enzyme inducers (e.g., CYP3A4): May decrease the effectiveness of levonorgestrel and ethinyl estradiol tablets or increase breakthrough bleeding.
Counsel patients to use a back-up or alternative method of contraception when enzyme inducers are used with levonorgestrel and ethinyl estradiol tablets. ( 7.1 )
7.1Effects of Other Drugs on Combined Oral Contraceptives Substances decreasing the plasma concentrations of COCs and potentially diminishing the efficacy of COCs: Table 5 includes substances that demonstrated an important drug interaction with levonorgestrel and ethinyl estradiol tablets. Table 5: Significant Drug Interactions Involving Substances That Affect COCs Metabolic Enzyme Inducers Clinical effect Concomitant use of COCs with metabolic enzyme inducers may decrease the plasma concentrations of the estrogen and/or progestin component of COCs.
Decreased exposure of the estrogen and/or progestin component of COCs may potentially diminish the effectiveness of COCs and may lead to contraceptive failure or an increase in breakthrough bleeding. Prevention or management Counsel females to use an alternative method of contraception or a backup method when enzyme inducers are used with COCs. Continue backup contraception for 28 days after discontinuing the enzyme inducer to maintain contraceptive reliability.
Examples Aprepitant, barbiturates, bosentan, carbamazepine, efavirenz, felbamate, griseofulvin, oxcarbazepine, phenytoin, rifampin, rifabutin, rufinamide, topiramate, products containing St. John’s wort a , and certain protease inhibitors (see separate section on protease inhibitors below). Colesevelam Clinical effect Concomitant use of COCs with colesevelam significantly decreases systemic exposure of ethinyl estradiol [see Clinical Pharmacology (12.3) ] .
Decreased exposure of the estrogen component of COCs may potentially reduce contraceptive efficacy or result in an increase in breakthrough bleeding, depending on the strength of ethinyl estradiol in the COC. Prevention or management Administer 4 or more hours apart to attenuate this drug interaction. a Induction potency of St. John’s wort may vary widely based on preparation.
Substances increasing the systemic exposure of COCs: Co-administration of atorvastatin or rosuvastatin and certain COCs containing ethinyl estradiol (EE) increase AUC values for EE by approximately 20-25%. Ascorbic acid and acetaminophen may increase systemic exposure of EE possibly by inhibition of conjugation. CYP3A4 inhibitors such as itraconazole, voriconazole, fluconazole, grapefruit juice, or ketoconazole may increase systemic exposure of estrogen and/or progestin component of COCs.
Human immunodeficiency virus (HIV)/ Hepatitis C virus (HCV) protease inhibitors and non-nucleoside reverse transcriptase inhibitors: Significant decreases in systemic exposure of the estrogen and/or progestin have been noted when COCs are co-administered with some HIV protease inhibitors (e.g., nelfinavir, ritonavir, darunavir/ritonavir, (fos)amprenavir/ritonavir, lopinavir/ritonavir, and tipranavir/ritonavir] or some HCV protease inhibitors (e.g., boceprevir and telaprevir) and some non-nucleosidase reverse transcriptase inhibitors (e.g., nevirapine).
In contrast, significant increases in syst…
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS Pregnancy: Discontinue if pregnancy occurs. ( 8.1 ) Lactation: Advise use of another contraceptive method; levonorgestrel and ethinyl estradiol tablets; may decrease milk production. ( 8.2 )
8.1Pregnancy Risk Summary There is no use for contraception in pregnancy; therefore, levonorgestrel and ethinyl estradiol tablets should be discontinued during pregnancy. Epidemiologic studies and meta-analyses have not found an increased risk of genital or non-genital birth defects (including cardiac anomalies and limb-reduction defects) following exposure to COCs before conception or during early pregnancy. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4 percent and 15 to 20 percent, respectively.
8.2Lactation Risk Summary Contraceptive hormones and/or metabolites are present in human milk. COCs can reduce milk production in breastfeeding females. This reduction can occur at any time but is less likely to occur once breastfeeding is well-established.
When possible, advise the nursing female to use other methods of contraception until she discontinues breastfeeding [see Dosage and Administration (2.1) ] . The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for levonorgestrel and ethinyl estradiol tablets and any potential adverse effects on the breastfed child from levonorgestrel and ethinyl estradiol tablets or the underlying maternal condition.
8.4Pediatric Use Safety and efficacy of levonorgestrel and ethinyl estradiol tablets have been established in women of reproductive age. Efficacy is expected to be the same for postpubertal adolescents under the age of 18 as for users 18 years and older. Use of levonorgestrel and ethinyl estradiol tablets before menarche is not indicated.
8.5Geriatric Use Levonorgestrel and ethinyl estradiol tablets have not been studied in postmenopausal women and is not indicated in this population.
8.6Hepatic Impairment The pharmacokinetics of levonorgestrel and ethinyl estradiol tablets have not been studied in subjects with hepatic impairment. However, COCs may be poorly metabolized in patients with hepatic impairment. Levonorgestrel and ethinyl estradiol tablets are contraindicated in females with acute hepatitis or severe decompensated cirrhosis [see Contraindications (4) and Warnings and Precautions (5.2) ] .
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary There is no use for contraception in pregnancy; therefore, levonorgestrel and ethinyl estradiol tablets should be discontinued during pregnancy. Epidemiologic studies and meta-analyses have not found an increased risk of genital or non-genital birth defects (including cardiac anomalies and limb-reduction defects) following exposure to COCs before conception or during early pregnancy. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4 percent and 15 to 20 percent, respectively.
🧒 Pediatric Use ▾
8.4Pediatric Use Safety and efficacy of levonorgestrel and ethinyl estradiol tablets have been established in women of reproductive age. Efficacy is expected to be the same for postpubertal adolescents under the age of 18 as for users 18 years and older. Use of levonorgestrel and ethinyl estradiol tablets before menarche is not indicated.
🧓 Geriatric Use ▾
8.5Geriatric Use Levonorgestrel and ethinyl estradiol tablets have not been studied in postmenopausal women and is not indicated in this population.
🆘 Overdosage ▾
10 OVERDOSAGE There have been no reports of serious ill effects from overdose of oral contraceptives, including ingestion by children. Overdosage may cause withdrawal bleeding in females and nausea.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action COCs prevent pregnancy primarily by suppressing ovulation.
12.2Pharmacodynamics No specific pharmacodynamic studies were conducted with Introvale.
12.3Pharmacokinetics Absorption No specific investigation of the absolute bioavailability of Introvale in humans has been conducted. However, literature indicates that levonorgestrel is rapidly and completely absorbed after oral administration (bioavailability nearly 100%) and is not subject to first-pass metabolism. EE is rapidly and almost completely absorbed from the gastrointestinal tract but, due to first-pass metabolism in gut mucosa and liver, the bioavailability of EE is approximately 43%.
Following continuous dosing with once-daily administration of Introvale tablets, plasma concentrations of levonorgestrel and EE reached steady-state within 7 days. The mean plasma pharmacokinetic parameters for Introvale under fasting conditions in normal healthy women following once-daily administration of one levonorgestrel/EE combination tablet for 10 days are summarized in Table 7. Table 7: Mean ±SD Pharmacokinetic Parameters Under Fasting Conditions in Healthy Women Following 10 Days Administration of One Tablet of Introvale (n=44) Analyte AUC 0-24 C max C min C avg a T max Levonorgestrel 54.6 ± 16.5 ng*hr/mL 5.0 ± 1.5 ng/mL 1.6 ± 0.5 ng/mL 2.3 ± 0.7 ng/mL 1.4 ± 0.7 hours Ethinyl estradiol 935.5 ± 346.9 pg*hr/mL 106.1 ± 41.2 pg/mL 18.5 ± 9.4 pg/mL 38.9 ± 14.4 pg/mL 1.6 ± 0.6 hours a C avg = AUC 0-24/24 Food Effect The effect of food on the rate and the extent of levonorgestrel and EE absorption following oral administration of Introvale has not been evaluated.
Distribution The apparent volume of distribution of levonorgestrel and EE are reported to be approximately
1.8 L/kg and
4.3L/kg, respectively. Levonorgestrel is about 97.5 - 99% protein-bound, principally to sex hormone binding globulin (SHBG) and, to a lesser extent, serum albumin. EE is about 95 - 97% bound to serum albumin.
EE does not bind to SHBG, but induces SHBG synthesis, which leads to decreased levonorgestrel clearance. Following repeated daily dosing of levonorgestrel/EE oral contraceptives, levonorgestrel plasma concentrations accumulate more than predicted based on single-dose pharmacokinetics, due in part, to increased SHBG levels that are induced by EE, and a possible reduction in hepatic metabolic capacity. Metabolism Following absorption, levonorgestrel is conjugated at the 17β-OH position to form sulfate and to a lesser extent, glucuronide conjugates in plasma.
Significant amounts of conjugated and unconjugated 3α,5β- tetrahydrolevonorgestrel are also present in plasma, along with much smaller amounts of 3α,5α- tetrahydrolevonorgestrel and 16β-hydroxylevonorgestrel. Levonorgestrel and its phase I metabolites are excreted primarily as glucuronide conjugates. Metabolic clearance rates may differ among individuals by several-fold, and this may account in part for the wide variation observed in levonorgestrel concentrations among users.
First-pass metabolism of EE involves formation of EE-3-sulfate in the gut wall, followed by 2-hydroxylation of a portion of the remaining untransformed EE by hepatic cytochrome P-450 3A4 (CYP3A4). Levels of CYP3A4 vary widely among individuals and can explain the variation in rates of EE hydroxylation. Hydroxylation at the 4-, 6-, and 16- positions may also occur, although to a much lesser extent than 2-hydroxylation.
The various hydroxylated metabolites are subject to further methylation and/or conjugation. Excretion About 45% of levonorgestrel and its metabolites are excreted in the urine and about 32% are excreted in feces, mostly as glucuronide conjugates. The terminal elimination half-life for levonorgestrel after a single dose of Introvale was about 30 hours.
EE is excreted in the urine and feces as glucuronide and sulfate conjugates, and it undergoes enterohepatic recirculation. The terminal elimination half-life of EE afte…
🧬 Mechanism of Action ▾
12.1Mechanism of Action COCs prevent pregnancy primarily by suppressing ovulation.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied Introvale (Levonorgestrel and Ethinyl Estradiol Tablets, USP) 0.15 mg/0.03 mg is available as round, biconvex, unscored tablets, packaged in a carton of 3 pouches (NDC 70700-208-88); each pouch (NDC 70700-208-87) contains Extended-Cycle Tablet Blister Pack of 91 tablets, each containing a 13-week supply of tablets: 84 white to off-white tablets, each containing 0.15 mg of levonorgestrel and 0.03 mg ethinyl estradiol: debossed with 212 on the one side and plain on the other side 7 green inert tablets debossed with 279 on the one side and plain on the other side Carton of 3 pouches NDC 70700-208-88 Storage and Handling Store at 20° to 25° C (68° to 77° F). [See USP Controlled Room Temperature.] Protect from light.
📋 Description ▾
11 DESCRIPTION Introvale (Levonorgestrel and Ethinyl Estradiol Tablets, USP) is an extended-cycle combination oral contraceptive consisting of 84 white to off-white active tablets each containing 0.15 mg of levonorgestrel, a synthetic progestin and 0.03 mg of ethinyl estradiol, an estrogen, and 7 green inert tablets (without hormones). The structural formulas for the active components are: Levonorgestrel is chemically 18,19-Dinorpregn-4-en-20-yn-3-one, 13-ethyl-17-hydroxy-, (17α)-, (-)-. Ethinyl Estradiol is 19-Norpregna-1,3,5(10)-trien-20-yne-3,17-diol, (17α)-.
Each white to off-white active tablet contains the following inactive ingredients: lactose monohydrate, magnesium stearate and polacrilin potassium. Each green inert tablet contains the following inactive ingredients: FD&C Blue No. 1 Aluminum Lake, lactose monohydrate, magnesium stearate, polacrilin potassium and yellow oxide of iron.
Levonorgestrel Stuctural Formula Ethinyl Estradiol Stuctural Formula
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling ( Patient Information and Instructions for Use ). Cigarette Smoking Cigarette smoking increases the risk of serious cardiovascular events from COC use. Women who are over 35 years old and smoke should not use Introvale [see Boxed Warning and Warnings and Precautions (5.1) ] .
Venous Thromboembolism The increased risk of VTE compared to non-users of COCs is greatest after initially starting a COC or restarting (following a 4-week or greater pill-free interval) the same or a different COC [see Warnings and Precautions (5.1) ] . Use During Pregnancy Instruct females to stop further intake of Introvale if pregnancy is confirmed during treatment. Sexually Transmitted Infections Introvale does not protect against HIV-infection (AIDS) and other sexually transmitted infections.
Dosing and Missed Pill Instructions Patients should take one tablet daily by mouth at the same time every day [see Dosage and Administration (2.1) ]. Instruct patients what to do in the event tablets are missed. See “What should I do if I miss any Introvale pills” section of FDA-Approved Instructions for Use [see Dosage and Administration (2.3) ].
Need for Additional Contraception Postpartum females who start Introvale who have not yet had a period when they start Introvale need to use an additional method of contraception until they have taken a white to off-white tablet for 7 consecutive days [see Dosage and Administration (2.1) ] . There is a need for a back-up or alternative method of contraception when enzyme inducers are used with Introvale [see Drug Interactions (7.1) ] . Lactation Introvale may reduce breast milk production.
This is less likely to occur if breastfeeding is well established. When possible, nursing women should use other methods of contraception until they have discontinued breastfeeding [see Use in Specific Populations (8.2) ] . Amenorrhea and Possible Symptoms of Pregnancy Amenorrhea may occur.
Because women using Introvale will likely have scheduled bleeding only 4 times per year, advise women to contact their health care provider in the event of amenorrhea with symptoms of pregnancy such as morning sickness or unusual breast tenderness [see Warnings and Precautions (5.9) ] . Depression Depressed mood and depression may occur. Women should contact their healthcare provider if mood changes and depressive symptoms occur, including shortly after initiating the treatment [see Warnings and Precautions (5.10) ] .