- norgestimate and ethinyl estradiol
A-S Medication Solutions
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use TRI-LO-MARZIA safely and effectively. See full prescribing information for TRI-LO-MARZIA
TRI-LO-MARZIA™ (norgestimate and ethinyl estradiol tablets USP), for oral use
Initial U.S. Approval: 1989
WARNING: CIGARETTE SMOKING and SERIOUS CARDIOVASCULAR EVENTS
See full prescribing information for complete boxed warning.
INDICATIONS AND USAGE
Tri-Lo-Marzia is an estrogen/progestin COC, indicated for use by women to prevent pregnancy. (1.1)
DOSAGE AND ADMINISTRATION
DOSAGE FORMS AND STRENGTHS
Tri-Lo-Marzia consists of 28 round, film-coated tablets in the following order (3):
WARNINGS AND PRECAUTIONS
The most common adverse reactions reported during clinical trials (≥2%) were: headache/migraine, nausea/vomiting, breast issues, abdominal pain, menstrual disorders, mood disorders, acne, vulvovaginal infection, abdominal distension, weight increased, fatigue. (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact Lupin Pharmaceuticals, Inc. at 1-800-399-2561 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Drugs or herbal products that induce certain enzymes including 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)
USE IN SPECIFIC POPULATIONS
Nursing mothers: Not recommended; can decrease milk production. (8.3)
See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling.
FULL PRESCRIBING INFORMATION: CONTENTS*
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)].
Tri-Lo-Marzia™ Tablets are indicated for use by females of reproductive potential to prevent pregnancy [see CLINICAL STUDIES (14)].
Tri-Lo-Marzia is dispensed in a wallet [see HOW SUPPLIED/STORAGE AND HANDLING (16)]. Tri-Lo-Marzia may be started using either a Day 1 start or a Sunday start (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 Tri-Lo-Marzia
|Starting COCs in women not currently using hormonal contraception (Day 1 Start or Sunday Start)
Consider the possibility of ovulation and conception prior to initiation of this product.
ο Tri-Lo-Marzia active tablets are white to off white (Day 1 to Day 7), light blue (Day 8 to Day 15) and blue (Day 16 to Day 21) and has green inactive tablets ( Day 22 to Day 28)
|Day 1 Start:
ο Take first active tablet without regard to meals on the first day of menses.
ο Take subsequent active tablets once daily at the same time each day for a total of 21 days.
ο Take one green inactive tablet daily for 7 days and at the same time of day that active tablets were taken.
ο Begin each subsequent pack on the same day of the week as the first cycle pack (i.e., on the day after taking the last inactive tablet)
ο Take first active tablet without regard to meals on the first Sunday after the onset of menses. Due to the potential risk of becoming pregnant, use additional non-hormonal contraception (such as condoms and spermicide) for the first seven days of the patient’s first cycle pack of Tri-Lo-Marzia.
ο Take subsequent active tablets once daily at the same time each day for a total of 21 days.
ο Take one green inactive tablet daily for the following 7 days and at the same time of day that active tablets were taken.
ο Begin each subsequent pack on the same day of the week as the first cycle pack (i.e., on the Sunday after taking the last inactive tablet) and additional non-hormonal contraceptive is not needed.
|Switching to Tri-Lo-Marzia 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 Tri-Lo-Marzia
|ο Transdermal patch
||ο On the day when next application would have been scheduled
|ο Vaginal ring
||ο On the day when next insertion would have been scheduled
||ο On the day when next injection would have been scheduled
|ο Intrauterine contraceptive
||ο On the day of removal
ο If the IUD is not removed on first day of the patient’s menstrual cycle, additional non-hormonal contraceptive (such as condoms and spermicide) is needed for the first seven days of the first cycle pack.
||ο On the day of removal
|Complete instructions to facilitate patient counseling on proper tablet usage are located in the FDA-Approved Patient Labeling.
Starting Tri-Lo-Marzia after Abortion or Miscarriage
Starting Tri-Lo-Marzia after Childbirth
SET THE DAY
|Table 2: Instructions for Missed Tri-Lo-Marzia Tablets
|Ο If one active tablet is missed in Weeks 1, 2, or 3||Take the tablet as soon as possible. Continue taking one tablet a day until the pack is finished.
|Ο If two active tablets are missed in Week 1 or Week 2||Take the two missed tablets as soon as possible and the next two active tablets the next day. Continue taking one tablet a day until the pack is finished. Additional non-hormonal contraception (such as condoms and spermicide) should be used as backup if the patient has sex within 7 days after missing tablets.
|Ο If two active tablets are missed in the third week or three or more active tablets are missed in a row in Weeks 1, 2, or 3||Day 1 start: Throw out the rest of the pack and start a new pack that same day.
Sunday start: Continue taking one tablet a day until Sunday, then throw out the rest of the pack and start a new pack that same day. Additional non-hormonal contraception (such as condoms and spermicide) should be used as back-up if the patient has sex within 7 days after missing 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 an active tablet, handle this as a missed tablet [see FDA-APPROVED PATIENT LABELING].
Tri-Lo-Marzia Tablets are available in a wallet. Each wallet contains 28 tablets in the following order:
Do not prescribe Tri-Lo-Marzia to women who are known to have the following conditions:
o Smoke, if over age 35 [see BOXED WARNING and WARNINGS AND PRECAUTIONS (5.1)]
o Have deep vein thrombosis or pulmonary embolism, now or in the past [see WARNINGS AND PRECAUTIONS (5.1)]
o Have inherited or acquired hypercoagulopathies [see WARNINGS AND PRECAUTIONS (5.1)]
o Have cerebrovascular disease [see WARNINGS AND PRECAUTIONS (5.1)]
o Have coronary artery disease [see WARNINGS AND PRECAUTIONS (5.1)]
o 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)]
o Have uncontrolled hypertension [see WARNINGS AND PRECAUTIONS (5.4)]
o Have diabetes mellitus with vascular disease [see WARNINGS AND PRECAUTIONS (5.6)]
o Have headaches with focal neurological symptoms or migraine headaches with aura [see WARNINGS AND PRECAUTIONS (5.7)]
o Women over age 35 with any migraine headaches [see WARNINGS AND PRECAUTIONS (5.7)]
Impaired Liver Function
Do not use Tri-Lo-Marzia in women with liver disease, such as acute viral hepatitis or severe (decompensated) cirrhosis of 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 Tri-Lo-Marzia if jaundice develops.
Tri-Lo-Marzia 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 risk of liver cancers in COC users is less than one case per million users.
Tri-Lo-Marzia 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 Tri-Lo-Marzia 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 with extended duration of use. The incidence of hypertension increases with increasing concentrations 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 take Tri-Lo-Marzia. 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 Tri-Lo-Marzia develops new headaches that are recurrent, persistent, or severe, evaluate the cause and discontinue Tri-Lo-Marzia if indicated.
Consider discontinuation of Tri-Lo-Marzia in the case of increased frequency or severity of migraine during COC use (which may be prodromal of a cerebrovascular event).
Unscheduled Bleeding and Spotting
Unscheduled (breakthrough or intracyclic) bleeding and spotting sometimes occur in patients on COCs, especially during the first three months of use. If bleeding persists or occurs after previously regular cycles, 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 contraceptive product.
In the clinical trial of Tri-Lo-Marzia, the frequency and duration of unscheduled bleeding and/or spotting was assessed in 1,673 women (11,015 evaluable cycles). A total of 3 (0.2%) women discontinued Tri-Lo-Marzia, at least in part, due to bleeding or spotting. Based on data from the clinical trials, 7 to 17% of women using Tri-Lo-Marzia experienced unscheduled bleeding per cycle in the first year. The percent of women who experienced unscheduled bleeding tended to decrease over time.
Amenorrhea and Oligomenorrhea
Women who use Tri-Lo-Marzia may experience amenorrhea. Some women may experience amenorrhea or oligomenorrhea after discontinuation of COCs, especially when such a condition was pre-existent.
If scheduled (withdrawal) bleeding does not occur, consider the possibility of pregnancy. If the patient has not adhered to the prescribed dosing schedule (missed one or more active tablets or started taking them on a day later than she should have), consider the possibility of pregnancy at the time of the first missed period and take appropriate diagnostic measures. If the patient has adhered to the prescribed regimen and misses two consecutive periods, rule out pregnancy.
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 Tri-Lo-Marzia use if pregnancy is confirmed.
Administration of COCs to induce withdrawal bleeding should not be used as a test for pregnancy [see USE IN SPECIFIC POPULATIONS (8.1)].
Carefully observe women with a history of depression and discontinue Tri-Lo-Marzia if depression recurs to a serious degree.
There is substantial evidence that COCs do not increase the incidence of breast cancer. Although some past studies have suggested that COCs might increase the incidence of breast cancer, more recent studies have not confirmed such findings.
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 healthcare.
In women with hereditary angioedema, exogenous estrogens may induce or exacerbate symptoms of angioedema.
The following serious adverse reactions with the use of COCs are discussed elsewhere in 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 rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
The safety of Tri-Lo-Marzia was evaluated in 1,723 subjects who participated in a randomized, partially blinded, multicenter, active-controlled clinical trial of Tri-Lo-Marzia for contraception. This trial examined healthy, nonpregnant, volunteers aged 18 to 45 (nonsmoker if 35 to 45 years of age), who were sexually active with regular coitus. Subjects were followed for up to 13 28-day cycles.
Common Adverse Reactions (≥ 2% of subjects)
The most common adverse reactions reported by at least 2% of the 1,723 women using the 28-day regimen were the following in order of decreasing incidence: headache/migraine (30.5%), nausea/vomiting (16.3%); breast issues (including tenderness, pain, enlargement, swelling, discharge, discomfort, cyst, and nipple pain) (10.3%), abdominal pain (9.2%), menstrual disorders (including dysmenorrhea, menstrual discomfort, menstrual disorder) (9.2%), mood disorders (including depression, mood altered, mood swings and depressed mood) (7.6%); acne (5.1%), vulvovaginal infection (3.5%), abdominal distension (2.8%), weight increased (2.4%), fatigue (2.1%).
Adverse Reactions Leading to Study Discontinuation
In the clinical trial of Tri-Lo-Marzia 4% of subjects discontinued the trial due to an adverse reaction. The most common adverse reactions leading to discontinuation were headache/migraine (1.2%), nausea/vomiting (0.7%), cervical dysplasia (0.7%), abdominal pain (0.4%), ovarian cyst (0.3%), acne (0.2%), flatulence (0.2%) and depression (0.2%).
Serious Adverse Reactions
Carcinoma of the cervix in situ (1 subject) and cervical dysplasia (1 subject).
The following additional adverse drug reactions have been reported from worldwide postmarketing experience with norgestimate/ethinyl estradiol. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Infections and Infestations
Urinary tract infection
Neoplasms Benign, Malignant and Unspecified (Including Cysts and Polyps)
Breast cancer, benign breast neoplasm, hepatic adenoma, focal nodular hyperplasia, breast cyst
Immune System Disorders
Metabolism and Nutrition Disorders
Nervous System Disorders
Syncope, convulsion, paresthesia, dizziness
Visual impairment, dry eye, contact lens intolerance
Ear and Labyrinth Disorders
Deep vein thrombosis, pulmonary embolism, retinal vascular thrombosis, hot flush
Arterial thromboembolism, myocardial infarction, cerebrovascular accident
Respiratory, Thoracic and Mediastinal Disorders
Pancreatitis, abdominal distension, diarrhea, constipation
Skin and Subcutaneous Tissue Disorders
Angioedema, erythema nodosum, hirsutism, night sweats, hyperhidrosis, photosensitivity reaction, urticaria, pruritus, acne
Musculoskeletal, Connective Tissue, and Bone Disorders
Muscle spasms, pain in extremity, myalgia, back pain
Reproductive System and Breast Disorders
Ovarian cyst, suppressed lactation, vulvovaginal dryness
General Disorders and Administration Site Conditions
Chest pain, asthenic conditions.
Consult the labeling of concurrently used drugs to obtain further information about interactions with hormonal contraceptives or the potential for enzyme alterations.
No drug-drug interaction studies were conducted with Tri-Lo-Marzia.
Substances Decreasing the Plasma Concentrations 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 COCs include phenytoin, barbiturates, carbamazepine, bosentan, felbamate, griseofulvin, oxcarbazepine, rifampicin, topiramate, rifabutin, rufinamide, aprepitant and products containing St. John's wort. Interactions between COCs 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, a bile acid sequestrant, given together with a COC, has been shown to significantly decrease the AUC of ethinyl estradiol (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 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., boceprevir and telaprevir]) or with non-nucleoside reverse transcriptase inhibitors (decrease [e.g., nevirapine] or increase [e.g., etravirine]).
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.
The use of contraceptive steroids may influence the results of certain laboratory tests, such as coagulation factors, lipids, glucose tolerance, and binding proteins.
Do not co-administer Tri-Lo-Marzia Tablets with HCV drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, due to potential for ALT elevations [see WARNINGS AND PRECAUTIONS (5.3)].
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 Tri-Lo-Marzia Tablets have been established in women of reproductive age. Efficacy is expected to be the same for post-pubertal adolescents under the age of 18 and for users 18 years and older. Use of this product before menarche is not indicated.
Tri-Lo-Marzia has not been studied in postmenopausal women and is not indicated in this population.
The pharmacokinetics of Tri-Lo-Marzia has 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).]
Tri-Lo-Marzia is a combination oral contraceptive containing the progestational compound norgestimate and the estrogenic compound ethinyl estradiol. Norgestimate is designated as ((+)-13-Ethyl-17-hydroxy-18, 19-dinor-17a-pregn-4-en-20-yn-3-one oxime acetate (ester)) and ethinyl estradiol is designated as (19-nor-17a-pregna,1,3,5(10)-trien-20-yne-3,17-diol).
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.
Norgestimate (NGM) and EE are rapidly absorbed following oral administration. NGM is rapidly and completely metabolized by first pass (intestinal and/or hepatic) mechanisms to norelgestromin (NGMN) and norgestrel (NG), which are the major active metabolites of NGM.
Mean pharmacokinetic parameters for NGMN, NG and EE during three cycles of administration of Tri-Lo-Marzia are summarized in Table 3.
Peak serum concentrations of NGMN and EE were generally reached by 2 hours after administration of Tri-Lo-Marzia. Accumulation following multiple dosing of the 0.18 mg NGM / 0.025 mg EE dose is approximately 1.5 to 2 fold for NGMN and approximately 1.5 fold for EE compared with single dose administration, in agreement with that predicted based on linear kinetics of NGMN and EE. The pharmacokinetics of NGMN is dose proportional following NGM doses of 0.18 to 0.25 mg. Steady-state conditions for NGMN following each NGM dose and for EE were achieved during the three cycle study. Non-linear accumulation (4.5 to 14.5 fold) of NG was observed as a result of high affinity binding to SHBG, which limits its biological activity.
Table 3 Summary of NGMN, NG and EE pharmacokinetic parameters.
NC = not calculated
||AUC0 to 24h
|NGMN(† to ‡)
||0.91 (0.27)||1.8 (1.0)||5.86 (1.54)||NC
||1.42 (0.43)||1.8 (0.7)||11.3 (3.2)||NC
||1.57 (0.39)||1.8 (0.7)||13.9 (3.7)||NC
||1.82 (0.54)||1.5 (0.7)||16.1 (4.8)||28.1 (10.6)
|NG(† to ‡)
||0.32 (0.14)||2.0 (1.1)||2.44 (2.04)||NC
||1.64 (0.89)||1.9 (0.9)||27.9 (18.1)||NC
||2.11 (1.13)||4.0 (6.3)||40.7 (24.8)||NC
||2.79 (1.42)||1.7 (1.2)||49.9 (27.6)||36.4 (10.2)
||55.6 (18.1)||1.7 (0.5)||421 (118)||NC
||91.1 (36.7)||1.3 (0.3)||782 (329)||NC
||96.9 (38.5)||1.3 (0.3)||796 (273)||NC
||95.9 (38.9)||1.3 (0.6)||771 (303)||17.7 (4.4)
The effect of food on the pharmacokinetics of Tri-Lo-Marzia has not been studied.
NGMN and NG are highly bound (>97%) to serum proteins. NGMN is bound to albumin and not to SHBG, while NG is bound primarily to SHBG. EE is extensively bound (>97%) to serum albumin and induces an increase in the serum concentrations of SHBG.
NGM is extensively metabolized by first-pass mechanisms in the gastrointestinal tract and/or liver. NGM's primary active metabolite is NGMN. Subsequent hepatic metabolism of NGMN occurs and metabolites include NG, which is also active and various hydroxylated and conjugated metabolites. Although NGMN and its metabolites inhibit a variety of P450 enzymes in human liver microsomes, under the recommended dosing regimen, the in vivo concentrations of NGMN and its metabolites, even at the peak serum levels, are relatively low compared to the inhibitory constant (Ki). EE is also metabolized to various hydroxylated products and their glucuronide and sulfate conjugates.
Following 3 cycles of administration of Tri-Lo-Marzia, the mean (± SD) elimination half-life values, at steady-state, for NGMN, NG and EE were 28.1 (± 10.6) hours, 36.4 (± 10.2) hours and 17.7 (± 4.4) hours, respectively (Table 2). The metabolites of NGMN and EE are eliminated by renal and fecal pathways.
Use in Specific Populations
Effects of Body Weight, Body Surface Area, and Age:
The effects of body weight, body surface area, age and race on the pharmacokinetics of NGMN, NG and EE were evaluated in 79 healthy women using pooled data following single dose administration of NGM 0.18 or 0.25 mg / EE 0.025 mg tablets in four pharmacokinetic studies. Increasing body weight and body surface area were each associated with decreases in Cmax and AUC0 to 24h values for NGMN and EE and increases in CL/F (oral clearance) for EE. Increasing body weight by 10 kg is predicted to reduce the following parameters: NGMN Cmax by 9% and AUC0 to 24h by 19%, NG Cmax by 12% and AUC0 to 24h by 46%, EE Cmax by 13% and AUC0 to 24h by 12%. These changes were statistically significant. Increasing age was associated with slight decreases (6% with increasing age by 5 years) in Cmax and AUC0 to 24h for NGMN and were statistically significant, but there was no significant effect for NG or EE. Only a small to moderate fraction (5 to 40%) of the overall variability in the pharmacokinetics of NGMN and EE following Tri-Lo-Marzia Tablets may be explained by any or all of the above demographic parameters.
In an active controlled clinical trial lasting 12 months, 1,673 women, 18 to 45 years old completed 11,003 cycles of Tri-Lo-Marzia use and a total of 20 pregnancies were reported in Tri-Lo-Marzia users. The racial demographic of those treated with Tri-Lo-Marzia was: Caucasian (86%), African-American (6%), Asian (2%), and Other (6%). There were no exclusions on the basis of weight; the weight range for women treated was 90 to 240 lbs, with a mean weight of about 142 lbs. The pregnancy rate in women aged 18 to 35 years was approximately 2.6 pregnancies per 100 woman-years of use.
Tri-Lo-Marzia are available in a wallet (NDC 68180-837-11) containing 28 tablets packed in a pouch (NDC 68180-837-11). Such three pouches are packaged in a carton (NDC 68180-837-13).
Each wallet (28 tablets) contains in the following order:
See FDA-APPROVED PATIENT LABELING (PATIENT INFORMATION and INSTRUCTION FOR USE).
Counsel patients about the following information:
Lupin Pharmaceuticals, Inc.
Baltimore, Maryland 21202
Pithampur (M.P.) - 454 775
November 2017 ID#: 253434
(norgestimate and ethinyl estradiol tablets USP)
What is the most important information I should know about Tri-Lo-Marzia?
Do not use Tri-Lo-Marzia 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 Tri-Lo-Marzia?
Tri-Lo-Marzia is a birth control pill (oral contraceptive) used by women to prevent pregnancy.
How does Tri-Lo-Marzia 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 from the clinical study, about 3 out of 100 women may get pregnant during the first year they use Tri-Lo-Marzia.
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 Tri-Lo-Marzia?
Do not take Tri-Lo-Marzia if you:
If any of these conditions happen while you are taking Tri-Lo-Marzia, stop taking Tri-Lo-Marzia right away and talk to your healthcare provider. Use non-hormonal contraception when you stop taking Tri-Lo-Marzia.
What should I tell my healthcare provider before taking Tri-Lo-Marzia?
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.
Tri-Lo-Marzia may affect the way other medicines work, and other medicines may affect how well Tri-Lo-Marzia 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 Tri-Lo-Marzia?
Read the Instructions for Use at the end of this Patient Information.
What are the possible serious side effects of Tri-Lo-Marzia?
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 Tri-Lo-Marzia?
These are not all the possible side effects of Tri-Lo-Marzia. For more information, ask your healthcare provider or pharmacist.
You may report side effects to the FDA at 1-800-FDA-1088.
You may also report side effects to Lupin Pharmaceuticals, Inc. at 1-800-399-2561 or you can visit the Lupin website at www.lupinpharmaceuticals.com.
What else should I know about taking Tri-Lo-Marzia?
How should I store Tri-Lo-Marzia?
General information about the safe and effective use of Tri-Lo-Marzia.
Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use Tri-Lo-Marzia for a condition for which it was not prescribed. Do not give Tri-Lo-Marzia to other people, even if they have the same symptoms that you have.
This Patient Information summarizes the most important information about Tri-Lo-Marzia. You can ask your pharmacist or healthcare provider for information about Tri-Lo-Marzia that is written for health professionals.
For more information, call Lupin Pharmaceuticals, Inc. at 1-800-399-2561 or you can visit the Lupin website at www.lupinpharmaceuticals.com.
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 Tri-Lo-Marzia?
Your periods may be lighter and shorter than usual. Some women may miss a period. Irregular vaginal bleeding or spotting may happen while you are taking Tri-Lo-Marzia, especially during the first few months of use. This usually is not a serious problem. It is important to continue taking your pills on a regular schedule to prevent a pregnancy.
What are the ingredients in Tri-Lo-Marzia?
Active ingredients: Each white to off white, light blue, and blue pill contains norgestimate and ethinyl estradiol.
White to off white pills: anhydrous lactose, croscarmellose sodium, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, polyethylene glycol, povidone and titanium dioxide.
Light blue pills: anhydrous lactose, croscarmellose sodium, FD&C Blue No. 2 Aluminium Lake, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, polyethylene glycol, povidone and titanium dioxide.
Blue pills: anhydrous lactose, croscarmellose sodium, FD&C Blue No. 2 Aluminium Lake, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, polyethylene glycol, povidone and titanium dioxide.
Green pills: croscarmellose sodium, FD&C Blue No. 2 Aluminium Lake, hypromellose, iron oxide yellow, lactose monohydrate, magnesium stearate, microcrystalline cellulose, polyethylene glycol and titanium dioxide.
(norgestimate and ethinyl estradiol tablets USP)
Important Information about taking Tri-Lo-Marzia
Before you start taking Tri-Lo-Marzia:
When should I start taking Tri-Lo-Marzia?
If you start taking Tri-Lo-Marzia and you have not used a hormonal birth control method before:
If you start taking Tri-Lo-Marzia and you are switching from another birth control pill:
If you start taking Tri-Lo-Marzia and previously used a vaginal ring or transdermal patch:
If you start taking Tri-Lo-Marzia and you are switching from a progestin-only method such as an implant or injection:
If you start taking Tri-Lo-Marzia 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 Tri-Lo-Marzia?" above. Follow these instructions for either a Sunday Start or a Day 1 Start.
You will use a Sunday Start if your healthcare provider told you to take your first pill on a Sunday.
Day 1 Start:
You will use a Day 1 Start if your doctor told you to take your first pill (Day 1) on the first day of your period.
Instructions for using your wallet:
Each new wallet has 28 pills
Step 1. SET THE DAY on your Wallet
Sunday Start: Each wallet has been preprinted with the days of the week, starting with Sunday, to facilitate a Sunday-Start regimen.
Day 1 Start:
Step 2. Remove pill "1" by pushing down on the pill. The pill will come out through a hole in the back of the strip.
Step 3. Swallow the pill. You will take 1 pill every day, at the same time each day.
Step 4. Wait 24 hours to take your next pill. Continue to take 1 pill each day until all the pills have been taken.
Step 5. Take your pill at the same time every day. It is important to take the correct pill each day and not miss any pills.
To help you remember, take your pill at the same time as another daily activity, like turning off your alarm clock or brushing your teeth.
Step 6. When your wallet is empty. You will start a new wallet on the day after pill "28." Remember to take your first pill in every refill on the same day of the week, no matter when your next period starts.
What should I do if I miss any Tri-Lo-Marzia pills?
If you miss 1 pill in Weeks 1, 2, or 3, follow these steps:
If you miss 2 pills in Week 1 or Week 2 of your pack, follow these steps:
If you miss 2 pills in a row in Week 3, or you miss 3 or more pills in a row during Weeks 1, 2, or 3 of the pack, follow these steps:
If you have any questions or are unsure about the information in this leaflet, call your healthcare provider.
Lupin Pharmaceuticals, Inc.
Baltimore, Maryland 21202
Pithampur (M.P.) - 454 775
This Patient Information and Instructions for Use has been approved by the U.S. Food and Drug Administration.
November 2017 ID#: 253435
norgestimate and ethinyl estradiol kit
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