Introvale by is a Prescription medication manufactured, distributed, or labeled by Xiromed, LLC., XIROMED PHARMA ESPANA, S.L., Aspen Oss B.V.. Drug facts, warnings, and ingredients follow.
IntrovaleTM is an estrogen/progestin COC indicated for use by women to prevent pregnancy. (1)
IntrovaleTM (levonorgestrel and ethinyl estradiol tablets, USP) consists of 84 round, peach tablets containing 0.15 mg of levonorgestrel and 0.03 mg of ethinyl estradiol, and 7 round, white inert tablets. (3)
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 1-844-XIROMED (1-844-947-6639) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Drugs or herbal products that induce certain enzymes (for example CYP3A4) may decrease the effectiveness of COCs or increase breakthrough bleeding. Counsel patients to use a back-up or alternative method of contraception when enzyme inducers are used with COCs. (7.1)
See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling.
Revised: 2/2018
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 are contraindicated in women who are over 35 years of age and smoke [see Contraindications (4)].
IntrovaleTM is dispensed in an Extended-Cycle Blister Card [see How Supplied/Storage and Handling (16)]. IntrovaleTM 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.
Instruct patients to take IntrovaleTM once a day by mouth at the same time every day for 91 days. To achieve maximum contraceptive effectiveness, IntrovaleTM should be taken exactly as directed and at intervals not exceeding 24 hours. For patient instructions regarding missed pills, see FDA-approved patient labeling.
Table 1Instructions for Administration of IntrovaleTM
Starting COCs in women not currently using hormonal contraception (Sunday Start) Important: Consider the possibility of ovulation and conception prior to initiation of this product. Tablet Color:
|
Sunday Start: For each 91-day course, take in the following order:
|
Switching to IntrovaleTM from another oral contraceptive |
Start on the same day that a new pack of the previous oral contraceptive would have started. |
Switching from another contraceptive method to IntrovaleTM |
Start IntrovaleTM: |
|
On the day when the next application would have been scheduled. |
|
On the day when the next insertion would have been scheduled. |
|
On the day when the next injection would have been scheduled. |
|
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. days of the first 91-day course. |
|
On the day of removal. |
Complete instructions to facilitate patient counseling on proper tablet usage are located in the FDA-approved patient labeling. |
Starting IntrovaleTM after Abortion or Miscarriage
First-trimester
Second-trimester
Starting IntrovaleTM after Childbirth
Tablet Dispenser Instructions:
|
Take the tablet as soon as possible. Take the next tablet at the regular time and continue taking one tablet a day until the 91-day course is finished. |
|
Take 2 tablets on the day remembered and 2 tablets the next day. Then continue taking one tablet a day until the 91-day course is finished. Additional non-hormonal contraception(such as condoms or spermicide) should be used as back-up if the patient has sex within 7 days after missing 2 tablets. |
|
Do not take the missed tablets. Continue taking one tablet a day until the 91-day course is finished. Additional non-hormonal contraception (such as condoms or spermicide) must be used as back-up if the patient has sex within 7 days after missing 3 tablets. |
In case of severe vomiting or diarrhea, absorption may not be complete and additional contraceptive measures should be taken. If vomiting or diarrhea occurs within 3 to 4 hours after taking a peach tablet, handle this as a missed tablet [see FDA-approved patient labeling].
IntrovaleTM (levonorgestrel and ethinyl estradiol tablets) are available as round, film-coated, debossed “SZ” on one side, packaged in a unit carton, each containing a 13-week supply of tablets in the following order:
Do not prescribe IntrovaleTM (levonorgestrel and ethinyl estradiol tablets) to women who are known to have the following conditions:
Impaired Liver Function
Do not use levonorgestrel and ethinyl estradiol in women with liver disease, such as acute viral hepatitis or severe (decompensated) cirrhosis of the liver [see Contraindications (4)]. Acute or chronic disturbances of liver function may necessitate the discontinuation of COC use until markers of liver function return to normal and COC causation has been excluded. Discontinue levonorgestrel and ethinyl estradiol if jaundice develops.
Liver Tumors
Levonorgestrel and ethinyl estradiol is contraindicated in women with benign and malignant liver tumors [see Contraindications (4)]. Hepatic adenomas are associated with COC use. An estimate of the attributable risk is 3.3 cases/100,000 COC users. Rupture of hepatic adenomas may cause death through intra-abdominal hemorrhage. Studies have shown an increased risk of developing hepatocellular carcinoma in long-term (>8 years) COC users. However, the attributable risk of liver cancers in COC users is less than one case per million users.
During clinical trial with the Hepatitis C combination drug regimen that contains ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, ALT elevations greater than 5 times the upper limit of normal (ULN), including some cases greater than 20 times the ULN, were significantly more frequent in women using ethinyl streadiol-containing medications, such as COCs. Discontinue Introvale™ prior to starting therapy with the combination drug regimen ombitasvir/paritaprevir/ritonavir, with or without dasabuvir. Introvale™ can be restarted approximately 2 weeks following completion of treatment with Hepatitis C combination drug regimen.
Levonorgestrel and ethinyl estradiol is contraindicated in women with uncontrolled hypertension or hypertension with vascular disease [see Contraindications (4)]. For women with well-controlled hypertension, monitor blood pressure and stop levonorgestrel and ethinyl estradiol if blood pressure rises significantly.
An increase in blood pressure has been reported in women taking COCs, and this increase is more likely in older women and with extended duration of use. The incidence of hypertension increases with increasing concentration of progestin
Studies suggest a small increased relative risk of developing gallbladder disease among COC users. Use of COCs may worsen existing gallbladder disease.
A past history of COC-related cholestasis predicts an increased risk with subsequent COC use. Women with a history of pregnancy-related cholestasis may be at an increased risk for COC-related cholestasis.
Carefully monitor prediabetic and diabetic women who are taking levonorgestrel and ethinyl estradiol. COCs may decrease glucose tolerance.
Consider alternative contraception for women with uncontrolled dyslipidemia. A small proportion of women will have adverse lipid changes while on COCs.
Women with hypertriglyceridemia, or a family history thereof, may be at an increased risk of pancreatitis when using COCs.
If a woman taking levonorgestrel and ethinyl estradiol develops new headaches that are recurrent, persistent, or severe, evaluate the cause and discontinue levonorgestrel and ethinyl estradiol if indicated.
Consider discontinuation of levonorgestrel and ethinyl estradiol in the case of increased frequency or severity of migraine during COC use (which may be prodromal of a cerebrovascular event) [see Contraindications (4)].
Bleeding and/or spotting that occurs at any time while taking the first 84 tablets of each extended-cycle regimen is considered “unscheduled” bleeding/spotting. Bleeding that occurs during the time a woman takes the seven white inert tablets is considered “scheduled” bleeding.
Unscheduled and Scheduled Bleeding and Spotting
Unscheduled (breakthrough) bleeding and spotting sometimes occur in patients on COCs, especially during the first 3 months of use. If unscheduled bleeding persists or occurs after previously regular cycles on levonorgestrel and ethinyl estradiol, check for causes such as pregnancy or malignancy. If pathology and pregnancy are excluded, bleeding irregularities may resolve over time or with a change to a different COC.
Before prescribing levonorgestrel and ethinyl estradiol, advise the woman to weigh the convenience of fewer scheduled menses (4 per year instead of 13 per year) against the inconvenience of increased unscheduled bleeding and/or spotting.
The clinical trial of the efficacy of levonorgestrel and ethinyl estradiol (91-day cycles) in preventing pregnancy also assessed scheduled and unscheduled bleeding. The participants in the study were composed primarily of women who had used oral contraceptives previously as opposed to new users. Women with a history of breakthrough bleeding/spotting ≥ 10 consecutive days on oral contraceptives were excluded from the study. More levonorgestrel and ethinyl estradiol subjects, compared to subjects on the comparator 28-day cycle regimen, discontinued prematurely for unacceptable bleeding (7.7% [levonorgestrel and ethinyl estradiol] vs. 1.8% [28-day cycle regimen]).
Unscheduled bleeding and unscheduled spotting decreased over successive 91-day cycles. Table 3 below presents the number of days with unscheduled bleeding and/or spotting for each respective 91-day cycle.
Cycle (N) |
Days of Unscheduled Bleeding and/or Spotting per 84-Day Interval |
Median Days Per Subject- Month |
|||
Mean |
Q1 |
Median |
Q3 |
||
1 (446) |
15.1 |
3 |
12 |
23 |
3 |
2 (368) |
11.6 |
2 |
6 |
17.5 |
1.5 |
3 (309) |
10.6 |
1 |
6 |
15 |
1.5 |
4 (282) |
8.8 |
1 |
4 |
14 |
1 |
Q1=Quartile 1: 25% of women had ≤ this number of days of unscheduled bleeding/spotting
Median: 50% of women had ≤ this number of days of unscheduled bleeding/spotting
Q3=Quartile 3: 75% of women had ≤ this number of days of unscheduled bleeding/spotting
Table 4 shows the percentages of women with ≥7 days and ≥20 days of unscheduled spotting and/or bleeding in the levonorgestrel and ethinyl estradiol and the 28-day cycle treatment groups.
Days of unscheduled bleeding and/or spotting |
Percentage of Subjectsa |
|
Levonorgestrel and Ethinyl Estradiol |
Cycle 1 (N=385) |
Cycle 4 (N=261) |
≥7 days |
65% |
42% |
≥20 days |
35% |
15% |
28-day regimen |
Cycle 1-4 (N=194) |
Cycle 10-13 (N=158) |
≥7 days |
38% |
39% |
≥20 days |
6% |
4% |
aBased on spotting and/or bleeding on days 1 to 84 of a 91 day cycle in the levonorgestrel and ethinyl estradiol subjects and days 1 to 21 of a 28 day cycle over 4 cycles in the 28-day dosing regimen.
Total days of bleeding and/or spotting (scheduled plus unscheduled) were similar over one year of treatment for levonorgestrel and ethinyl estradiol subjects and subjects on the 28-day cycle regimen.
Amenorrhea and Oligomenorrhea
Women who are not pregnant and use levonorgestrel and ethinyl estradiol may experience amenorrhea. Based on data from the clinical trial, amenorrhea occurred in approximately 0.8% of women during Cycle 1, 1.2% of women during Cycle 2, 3.7% of women during Cycle 3, and 3.4% of women during Cycle 4. Because women using levonorgestrel and ethinyl estradiol will likely have scheduled bleeding only 4 times per year, rule out pregnancy at the time of any missed menstrual period.
Some women may experience amenorrhea or oligomenorrhea after stopping COCs, especially when such a condition was pre-existent.
Extensive epidemiological studies have revealed no increased risk of birth defects in women who have used oral contraceptives prior to pregnancy. Studies also do not suggest a teratogenic effect, particularly in so far as cardiac anomalies and limb-reduction defects are concerned, when oral contraceptives are taken inadvertently during early pregnancy. Discontinue levonorgestrel and ethinyl estradiol use if pregnancy is confirmed.
Administration of oral contraceptives to induce withdrawal bleeding should not be used as a test for pregnancy [see Use in Specific Populations (8.1)].
Depression associated with the use of levonorgestrel and ethinyl estradiol has been reported. Carefully observe women with a history of depression and discontinue levonorgestrel and ethinyl estradiol if severe depression recurs.
The estrogen component of COCs may raise the serum concentrations of thyroxine-binding globulin, sex hormone-binding globulin and cortisol-binding globulin. The dose of replacement thyroid hormone or cortisol therapy may need to be increased.
A woman who is taking COCs should have a yearly visit with her healthcare provider for a blood pressure check and for other indicated health care.
The following serious adverse reactions with the use of COCs are discussed elsewhere in the labeling:
Adverse reactions commonly reported by COC users are:
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 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 (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 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.
The following adverse reactions have been identified during post-approval use of levonorgestrel and ethinyl estradiol. 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, pulmonary thrombosis
Consult the labeling of concurrently used drugs to obtain further information about interactions with hormonal contraceptives or the potential for enzyme alterations.
Substances decreasing the plasma concentrations of COCs and potentially diminishing the efficacy of COCs
Drugs or herbal products that induce certain enzymes, including cytochrome P450 3A4 (CYP3A4), may decrease the plasma concentrations of COCs and potentially diminish the effectiveness of COCs or increase breakthrough bleeding. Some drugs or herbal products that may decrease the effectiveness of hormonal contraceptives include phenytoin, barbiturates, carbamazepine, bosentan, felbamate, griseofulvin, oxcarbazepine, rifampicin, topiramate, rifabutin, rufinamide, aprepitant, and products containing St. John’s wort. Interactions between oral contraceptives and other drugs may lead to breakthrough bleeding and/or contraceptive failure. Counsel women to use an alternative method of contraception or a back-up method when enzyme inducers are used with COCs, and to continue back-up contraception for 28 days after discontinuing the enzyme inducer to ensure contraceptive reliability.
Colesevelam
Colesevelam, a bile acid sequestrant, given together with a COC, has been shown to significantly decrease the AUC of EE. The drug interaction between the contraceptive and colesevelam was decreased when the two drug products were given 4 hours apart.
Substances increasing the plasma concentrations of COCs
Co-administration of atorvastatin or rosuvastatin and certain COCs containing ethinyl estradiol (EE) increase AUC values for EE by approximately 20 to 25%. Ascorbic acid and acetaminophen may increase plasma EE concentrations, possibly by inhibition of conjugation. CYP3A4 inhibitors such as itraconazole, voriconazole, fluconazole, grapefruit juice, or ketoconazole may increase plasma hormone concentrations.
Human immunodeficiency virus (HIV)/ Hepatitis C virus (HCV) protease inhibitors and non-nucleoside reverse transcriptase inhibitors
Significant changes (increase or decrease) in the plasma concentrations of estrogen and/or progestin have been noted in some cases of co-administration with HIV protease inhibitors(decrease [e.g., nelfinavir, ritonavir, darunavir/ritonavir, (fos)amprenavir/ritonavir, lopinavir/ritonavir, and tipranavir/ritonavir] or increase [e.g., indinavir and atazanavir/ritonavir])/HCV protease inhibitors (decrease [e.g., nevirapine] or increase [e.g., etravirine]).
COCs containing EE may inhibit the metabolism of other compounds (e.g., cyclosporine, prednisolone, theophylline, tizanidine, and voriconazole) and increase their plasma concentrations.
COCs have been shown to decrease plasma concentrations of acetaminophen, clofibric acid, morphine, salicylic acid, temazepam and lamotrigine. Significant decrease in plasma concentration of lamotrigine has been shown, likely due to induction of lamotrigine glucuronidation. This may reduce seizure control; therefore, dosage adjustments of lamotrigine may be necessary.
Women on thyroid hormone replacement therapy may need increased doses of thyroid hormone because the serum concentration of thyroid-binding globulin increases with use of COCs [see Warnings and Precautions (5.11)].
There is little or no increased risk of birth defects in women who inadvertently use COCs during early 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 low dose COCs prior to conception or during early pregnancy.
Do not administer COCs to induce withdrawal bleeding as a test for pregnancy. Do not use COCs during pregnancy to treat threatened or habitual abortion.
Advise the nursing mother to use other forms of contraception, when possible, until she has weaned her child. COCs can reduce milk production in breastfeeding mothers. This is less likely to occur once breastfeeding is well established; however, it can occur at any time in some women. Small amounts of oral contraceptive steroids and/or metabolites are present in breast milk.
Safety and efficacy of levonorgestrel and ethinyl estradiol 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 before menarche is not indicated.
Levonorgestrel and ethinyl estradiol has not been studied in postmenopausal women and is not indicated in this population.
The pharmacokinetics of levonorgestrel and ethinyl estradiol have not been studied in subjects with hepatic impairment. However, steroid hormones may be poorly metabolized in patients with hepatic impairment. Acute or chronic disturbances of liver function may necessitate the discontinuation of COC use until markers of liver function return to normal and COC causation has been excluded [see Contraindications (4) and Warnings and Precautions (5.2)].
IntrovaleTM (levonorgestrel and ethinyl estradiol tablets) is an extended-cycle combination oral contraceptive consisting of 84 peach active tablets each containing 0.15 mg of levonorgestrel, a synthetic progestin and 0.03 mg of ethinyl estradiol, an estrogen, and 7 white 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)-.
COCs lower the risk of becoming pregnant primarily by suppressing ovulation. Other possible mechanisms may include cervical mucus changes that inhibit sperm penetration and endometrial changes that reduce the likelihood of implantation.
No specific pharmacodynamic studies were conducted with levonorgestrel and ethinyl estradiol.
Absorption
No specific investigation of the absolute bioavailability of levonorgestrel and ethinyl estradiol 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 levonorgestrel and ethinyl estradiol tablets, plasma concentrations of levonorgestrel and EE reached steady-state within 7 days. The mean plasma pharmacokinetic parameters for levonorgestrel and ethinyl estradiol under fasting conditions in normal healthy women following once-daily administration of one levonorgestrel/EE combination tablet for 10 days are summarized in Table 5.
Table 5 Mean ±SD Pharmacokinetic Parameters Under Fasting Conditions in Healthy Women Following 10 Days Administration of One Tablet of Levonorgestrel and Ethinyl Estradiol (n=44)
Analyte |
AUC0-24 |
Cmax |
Cmin |
Cavga |
Tmax |
Levonorgestrel |
54.6±16.5 ng*hr/mL |
5±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 |
aCavg = AUC0-24/24
Food Effect
The effect of food on the rate and the extent of levonorgestrel and EE absorption following oral administration of levonorgestrel and ethinyl estradiol has not been evaluated.
Distribution
The apparent volume of distribution of levonorgestrel and EE are reported to be approximately 1.8 L/kg and 4.3 L/kg, respectively. Levonorgestrel is about 97.5 to 99% protein-bound, principally to sex hormone binding globulin (SHBG) and, to a lesser extent, serum albumin. EE is about 95 to 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 levonorgestrel and ethinyl estradiol 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 after a single dose of levonorgestrel and ethinyl estradiol was found to be about 15 hours.
In a 12-month, multicenter, randomized, open-label clinical trial, 456 women aged 18 to 40 were studied to assess the safety and efficacy of levonorgestrel and ethinyl estradiol, completing 809 91-day cycles of exposure. The racial demographic of those enrolled was: Caucasian (77%), African-American (11%), Hispanic (7%), Asian (2%), and Other (3%).
There were no exclusions for body mass index (BMI) or weight. The weight range of those women treated was 84 to 304 pounds, with a mean weight of 157 pounds and a median weight of 147 pounds. Among the women in the trial, 63% were current or recent hormonal contraceptive users, 29% were prior users (who had used hormonal contraceptives in the past but not in the 6 months prior to enrollment), and 8% were new starts.
The pregnancy rate (Pearl Index [PI]) in the 397 women aged 18 to 35 years was 1.98 pregnancies per 100 women-years of use (95% CI: 0.54 to 5.03), based on 4 pregnancies that occurred after the onset of treatment and within 14 days after the last combination pill. Cycles in which conception did not occur, but which included the use of back-up contraception, were not included in the calculation of the PI.
IntrovaleTM tablets (levonorgestrel and ethinyl estradiol, USP) are available in extended-cycle blister cards (NDC: 70700-117-87 ), each containing a 13-week supply of tablets: 84 peach active tablets, each containing 0.15 mg of levonorgestrel and 0.03 mg ethinyl estradiol, and 7 white inert tablets packaged in a unit carton. The active tablets are peach, round, film-coated, debossed “SZ”on one side and “J4”on the other side. The inert tablets are white, round, film-coated, debossed with “SZ” on one side and “J1” on the other side.
See FDA-approved patient labeling (Patient Information and Instructions for Use).
Counsel patients on the following information:
Manufactured by Laboratorios Leon Farma S.A., Spain
For Xiromed LLC, Florham Park NJ 07932
Product of Spain
Rev. February 2018
PI-117-00
IntrovaleTM
(levonorgestrel and ethinyl estradiol tablets, USP)
(lee-voe-nor-JES-trel ETH-in-il es-tra-DIE-ole)
What is the most important information I should know about IntrovaleTM?
Do not use IntrovaleTM if you smoke cigarettes and are over 35 years old. Smoking increases your risk of serious cardiovascular side effects from hormonal birth control pills, including death from heart attack, blood clots or stroke. This risk increases with age and the number of cigarettes you smoke.
What is IntrovaleTM?
IntrovaleTM is a birth control pill (oral contraceptive) used by women to prevent pregnancy.
How does IntrovaleTM work for contraception?
Your chance of getting pregnant depends on how well you follow the directions for taking your birth control pills. The better you follow the directions, the less chance you have of getting pregnant.
Based on the results of clinical studies, about 1 to 5 out of 100 women may get pregnant during the first year they use IntrovaleTM.
The following chart shows the chance of getting pregnant for women who use different methods of birth control. Each box on the chart contains a list of birth control methods that are similar in effectiveness. The most effective methods are at the top of the chart. The box on the bottom of the chart shows the chance of getting pregnant for women who do not use birth control and are trying to get pregnant.
Who should not take IntrovaleTM?
Do not take IntrovaleTM if you:
If any of these conditions happen while you are taking IntrovaleTM, stop taking IntrovaleTM right away and talk to your healthcare provider. Use non-hormonal contraception when you stop taking IntrovaleTM.
What should I tell my healthcare provider before taking IntrovaleTM?
Tell your healthcare provider if you:
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins and herbal supplements.
IntrovaleTM may affect the way other medicines work, and other medicines may affect how well IntrovaleTM works.
Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.
How should I take IntrovaleTM?
Read the Instructions for Use at the end of this Patient Information.
What are the possible serious side effects of IntrovaleTM?
Serious blood clots can happen especially if you smoke, are obese, or are older than 35 years of age. Serious blood clots are more likely to happen when you:
Call your healthcare provider or go to a hospital emergency room right away if you have:
Other serious side effects include:
What are the most common side effects of IntrovaleTM?
These are not all the possible side effects of IntrovaleTM. For more information, ask your healthcare provider or pharmacist.
You may report side effects to the FDA at 1-800-FDA-1088.
What else should I know about taking IntrovaleTM?
How should I store IntrovaleTM?
Store IntrovaleTM at room temperature between 68°F to 77°F (20°C to 25°C).
General information about the safe and effective use of IntrovaleTM.
Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use IntrovaleTM for a condition for which it was not prescribed. Do not give IntrovaleTM to other people, even if they have the same symptoms that you have.
This Patient Information summarizes the most important information about IntrovaleTM. You can ask your pharmacist or healthcare provider for information about IntrovaleTM that is written for health professionals.
For more information, call Xiromed, LLC. at 1-844-XIROMED (844-947-6633).
Do birth control pills cause cancer?
Birth control pills do not seem to cause breast cancer. However, if you have breast cancer now, or have had it in the past, do not use birth control pills because some breast cancers are sensitive to hormones.
Women who use birth control pills may have a slightly higher chance of getting cervical cancer. However, this may be due to other reasons such as having more sexual partners.
What if I want to become pregnant?
You may stop taking the pill whenever you wish. Consider a visit with your healthcare provider for a pre-pregnancy checkup before you stop taking the pill.
What should I know about my period when taking IntrovaleTM?
When you take IntrovaleTM, which has a 91-day extended dosing cycle, you should have 4 scheduled periods a year (bleeding when you are taking the 7 white pills). However, you will probably have more bleeding or spotting between your scheduled periods than if you were using a birth control pill with a 28-day dosing cycle. During the first IntrovaleTM 91-day treatment cycle, about 1 in 3 women may have 20 or more days of unplanned bleeding or spotting. This bleeding or spotting tends to decrease with time. Do not stop taking IntrovaleTM because of this bleeding or spotting. If the spotting continues for more than 7 days in a row or if the bleeding is heavy, call your healthcare provider.
What are the ingredients in IntrovaleTM?
Active ingredients: Each peach pill contains levonorgestrel and ethinyl estradiol.
Inactive ingredients:
Peach pills: lactose anhydrous, magnesium stearate, povidone, polyvinyl alcohol, polyethylene glycol, titanium dioxide, talc, iron oxide yellow, iron oxide red and iron oxide black.
White pills: lactose anhydrous, magnesium stearate, povidone, polyvinyl alcohol, polyethylene glycol, talc and titanium dioxide.
IntrovaleTM
(levonorgestrel and ethinyl estradiol tablets, USP)
(lee-voe-nor-JES-trel ETH-in-il es-tra-DIE-ole)
Important Information about taking IntrovaleTM
Before you start taking IntrovaleTM:
When should I start taking IntrovaleTM?
If you start taking IntrovaleTM and you have not used a hormonal birth control method before:
If you start taking IntrovaleTM and you are switching from another birth control pill:
If you start taking IntrovaleTM and previously used a vaginal ring:
If you start taking IntrovaleTM and previously used a transdermal patch:
If you start taking IntrovaleTM and you are switching from a progestin-only method such as an implant or injection:
If you start taking IntrovaleTM and you are switching from an intrauterine device or system (IUD or IUS):
Keep a calendar to track your period: If this is the first time you are taking birth control pills, read, “When should I start taking IntrovaleTM?” above. Follow these instructions for a Sunday Start.
Instructions for using your IntrovaleTM Extended-Cycle Blister Cards:
Sunday Start:
Take pill 1 on the Sunday after your period starts. To remove your pill from the dispenser, press the pill through the hole in the bottom of the dispenser. See Figure C.
Figure C
What should I do if I miss any IntrovaleTM pills?
If you miss 1 peach pill, follow these steps:
This means you may take 2 pills in 1 day.
If you miss 2 peach pills in a row, follow these steps:
If you miss 3 or more peach pills in a row, follow these steps:
If you have any questions or are unsure about the information in this leaflet, call your healthcare provider.
This Patient Information and Instructions for Use have been approved by the U.S. Food and Drug Administration.
Manufactured by Laboratorios Leon Farma S.A., Spain
For Xiromed LLC, Florham Park NJ 07932
Product of Spain
PIL-117-00
INTROVALE
levonorgestrel and ethinyl estradiol kit |
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Labeler - Xiromed, LLC. (080228637) |
Registrant - XIROMED PHARMA ESPANA, S.L. (468835741) |
Establishment | |||
Name | Address | ID/FEI | Business Operations |
---|---|---|---|
Aspen Oss B.V. | 491013870 | api manufacture(70700-117) |
Establishment | |||
Name | Address | ID/FEI | Business Operations |
---|---|---|---|
Aspen Oss B.V. | 491017488 | api manufacture(70700-117) |
Mark Image Registration | Serial | Company Trademark Application Date |
---|---|
INTROVALE 77850557 3998834 Live/Registered |
XIROMED PHARMA ESPAÃA S.L. 2009-10-16 |