TRI-LO-MILI- norgestimate and ethinyl estradiol
Proficient Rx LP
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HIGHLIGHTS OF PRESCRIBING INFORMATIONThese highlights do not include all the information needed to use TRI-LO-MILI® safely and effectively. See full prescribing information for TRI-LO-MILI.
TRI-LO-MILI (norgestimate and ethinyl estradiol) tablets for oral use Initial U.S. Approval: 1989 WARNING: CIGARETTE SMOKING and SERIOUS CARDIOVASCULAR EVENTSSee full prescribing information for complete boxed warning.RECENT MAJOR CHANGESWarnings and Precautions (5.11) 11/2021 INDICATIONS AND USAGETri-Lo-Mili (norgestimate and ethinyl estradiol tablets) is an estrogen/progestin COC, indicated for use by women to prevent pregnancy. (1.1) DOSAGE AND ADMINISTRATIONDOSAGE FORMS AND STRENGTHSTri-Lo-Mili (norgestimate and ethinyl estradiol tablets USP) consists of 21 round, biconvex, coated tablets and 7 round, mottled, biconvex, uncoated tablets in the following order (3):
CONTRAINDICATIONS
WARNINGS AND PRECAUTIONS
ADVERSE REACTIONSThe 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 Aurobindo Pharma USA, Inc. at 1-866-850-2876 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. DRUG INTERACTIONSDrugs 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 POPULATIONSNursing mothers: Not recommended; can decrease milk production. (8.3) See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling. Revised: 1/2023 |
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-Mili (norgestimate and ethinyl estradiol tablets) is indicated for use by females of reproductive potential to prevent pregnancy [see Clinical Studies (14)].
Tri-Lo-Mili (norgestimate and ethinyl estradiol tablets) is dispensed in a blister pack [see How Supplied/Storage and Handling (16)]. Tri-Lo-Mili (norgestimate and ethinyl estradiol tablets) 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-Mili (norgestimate and ethinyl estradiol tablets)
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Starting COCs in women not currently using hormonal contraception (Day 1 Start or Sunday Start)
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Day 1 Start:
Sunday Start:
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Switching to Tri-Lo-Mili (norgestimate and ethinyl estradiol tablets) from another oral contraceptive
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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-Mili (norgestimate and ethinyl estradiol tablets)
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Start Tri-Lo-Mili (norgestimate and ethinyl estradiol tablets):
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Complete instructions to facilitate patient counseling on proper tablet usage are located in the FDA-Approved Patient Labeling.
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Starting Tri-Lo-Mili (norgestimate and ethinyl estradiol tablets) after Abortion or Miscarriage
First-trimester
Second-trimester
Starting Tri-Lo-Mili (norgestimate and ethinyl estradiol tablets) after Childbirth
Blister Pack:
1. Decide what time of day you want to take your pill.
It is important to take it at about the same time every day.
2. The 28-pill pack has 21 white to off white, pale blue to bluish white, and blue to light blue “active” pills (with hormones) to take for 3 weeks. This is followed by 1 week of green “reminder” pills (without hormones).
3. Also find:
1) where on the pack to start taking pills,
2) in what order to take the pills, and
3) the week numbers as shown in the picture below.
4. Be sure you have ready at all times:
Another kind of birth control (such as condoms or spermicide) to use as a back-up method in case you miss pills.
An extra, full pill pack.
You have a choice of which day to start taking your first pack of pills. Tri-Lo-Mili is available in a blister pack which is preset for a Sunday Start. Day 1 Start stickers are also provided. Decide with your healthcare professional which is the best day for you. Pick a time of day that will be easy to remember.
Sunday Start:
Take the first white to off white “active” pill of the first pack on the Sunday after your period starts, even if you are still bleeding. If your period begins on Sunday, start the pack that same day.
Use another method of birth control (such as condoms or spermicide) as a back-up method if you have sex anytime from the Sunday you start your first pack until the next Sunday (7 days).
Day 1 Start:
Take the first white to off white "active" pill of the first pack during the first 24 hours of your period.
Note: If the first day of your period is a Sunday, you can skip steps #1 and #2.
You will not need to use a back-up method of birth control, since you are starting the pill at the beginning of your period.
Table 2: Instructions for Missed Tri-Lo-Mili (norgestimate and ethinyl estradiol tablets)
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Take the tablet as soon as possible. Continue taking one tablet a day until the pack is finished. |
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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 back-up if the patient has sex within 7 days after missing tablets.
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Day 1 start: Throw out the rest of the pack and start a new pack that same day. |
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-Mili (norgestimate and ethinyl estradiol tablets USP) is available in a blister pack. Each blister pack contains 28 tablets in the following order:
Tri-Lo-Mili (norgestimate and ethinyl estradiol tablets) is contraindicated in females who are known to have or develop the following conditions:
Impaired Liver Function
Do not use Tri-Lo-Mili 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-Mili if jaundice develops.
Liver Tumors
Tri-Lo-Mili 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.
During clinical trials 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 estradiol-containing medications, such as COCs. Discontinue Tri-Lo-Mili prior to starting therapy with the combination drug regimen ombitasvir/paritaprevir/ritonavir, with or without dasabuvir [see Contraindications (4)]. Tri-Lo-Mili can be restarted approximately 2 weeks following completion of treatment with the Hepatitis C combination drug regimen.
Tri-Lo-Mili 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-Mili 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-Mili. 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-Mili develops new headaches that are recurrent, persistent, or severe, evaluate the cause and discontinue Tri-Lo-Mili if indicated.
Consider discontinuation of Tri-Lo-Mili 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-Mili, 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-Mili, at least in part, due to bleeding or spotting. Based on data from the clinical trials, 7 to 17% of women using Tri-Lo-Mili 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-Mili 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-Mili 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-Mili if depression recurs to a serious degree.
Breast Cancer
Tri-Lo-Mili is contraindicated in females who currently have or have had breast cancer because breast cancer may be hormonally sensitive [see Contraindications (4)].
Epidemiology studies have not found a consistent association between use of combined oral contraceptives (COCs) and breast cancer risk. Studies do not show an association between ever (current or past) use of COCs and risk of breast cancer. However, some studies report a small increase in the risk of breast cancer among current or recent users (<6 months since last use) and current users with longer duration of COC use [see Postmarketing Experience (6.2)].
Cervical Cancer
A causal relationship between the use of CHCs and the development of cervical cancer and intraepithelial neoplasia has not been clearly established. In observational studies, some studies suggest that COC use has been associated with an increase in the risk of cervical cancer or intraepithelial neoplasia. However, there continues to be controversy about the extent to which such findings may be due to differences in sexual behavior and other factors.
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.
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-Mili was evaluated in 1,723 subjects who participated in a randomized, partially blinded, multicenter, active-controlled clinical trial of Tri-Lo-Mili 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-Mili 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).
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 to 1.12 (Figure 1).
Three studies compared breast cancer risk between current or recent COC users (<6 months since last use) and never users of COCs (Figure 1). 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 to 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 to 10 years of COC use.
Figure 1: Risk of Breast Cancer with Combined Oral Contraceptive Use
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 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: Hypersensitivity
Metabolism and Nutrition Disorders: Dyslipidemia
Psychiatric Disorders: Anxiety, insomnia
Nervous System Disorders: Syncope, convulsion, paresthesia, dizziness
Eye Disorders: Visual impairment, dry eye, contact lens intolerance
Ear and Labyrinth Disorders: Vertigo
Cardiac Disorders: Tachycardia, palpitations
Vascular Events: Deep vein thrombosis, pulmonary embolism, retinal vascular thrombosis, hot flush
Arterial Events: Arterial thromboembolism, myocardial infarction, cerebrovascular accident
Respiratory, Thoracic and Mediastinal Disorders: Dyspnea
Gastrointestinal Disorders: Pancreatitis, abdominal distension, diarrhea, constipation
Hepatobiliary Disorders: Hepatitis
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-Mili.
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: 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-Mili 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-Mili 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-Mili has not been studied in postmenopausal women and is not indicated in this population.
The pharmacokinetics of Tri-Lo-Mili 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).]
There have been no reports of serious ill effects from overdosage of oral contraceptives, including ingestion by children. Overdosage may cause withdrawal bleeding in females and nausea.
Tri-Lo-Mili is a combination oral contraceptive containing the progestational compound norgestimate and the estrogenic compound ethinyl estradiol. Norgestimate is designated as (18,19-Dinor-17-pregn-4-en-20-yn-3-one,17-(acetyloxy)-13-ethyl-, oxime, (17α)-(+)-) and ethinyl estradiol is designated as (19-nor-17α-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.
Absorption
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-Mili are summarized in Table 3.
Peak serum concentrations of NGMN and EE were generally reached by 2 hours after administration of Tri-Lo-Mili. Accumulation following multiple dosing of the 0.180 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 0.180 to 0.250 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.
1 NGMN = Norelgestromin, NG = norgestrel, EE = ethinyl estradiol 2 Cmax = peak serum concentration, tmax = time to reach peak serum concentration, AUC0-24h = area under serum concentration vs. time curve from 0 to 24 hours, t1/2 = elimination half-life. 3 units for all analytes; h = hours 4 units for NGMN and NG – Cmax = ng/mL, AUC0-24h = h•ng/mL 5 units for EE only – Cmax = pg/mL, AUC0-24h = h•pg/mL NC = not calculated |
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Analyte1
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Cycle |
Day |
Cmax
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tmax(h) |
AUC0-24h
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t1/2(h) |
NGMN(2-4)
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1
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1
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0.91 (0.27) |
1.8 (1) |
5.86 (1.54) |
NC
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3
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7
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1.42 (0.43) |
1.8 (0.7) |
11.3 (3.2) |
NC
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14
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1.57 (0.39) |
1.8 (0.7) |
13.9 (3.7) |
NC
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21
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1.82 (0.54) |
1.5 (0.7) |
16.1 (4.8) |
28.1 (10.6) |
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NG(2-4)
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1
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1
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0.32 (0.14) |
2 (1.1) |
2.44 (2.04) |
NC
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3
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7
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1.64 (0.89) |
1.9 (0.9) |
27.9 (18.1) |
NC
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14
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2.11 (1.13) |
4 (6.3) |
40.7 (24.8) |
NC
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21
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2.79 (1.42) |
1.7 (1.2) |
49.9 (27.6) |
36.4 (10.2) |
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EE(2,3,5)
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1
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1
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55.6 (18.1) |
1.7 (0.5) |
421 (118) |
NC
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3
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7
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91.1 (36.7) |
1.3 (0.3) |
782 (329) |
NC
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14
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96.9 (38.5) |
1.3 (0.3) |
796 (273) |
NC
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21
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95.9 (38.9) |
1.3 (0.6) |
771 (303) |
17.7 (4.4) |
Food Effect
The effect of food on the pharmacokinetics of Tri-Lo-Mili has not been studied.
Distribution
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.
Metabolism
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.
Excretion
Following 3 cycles of administration of Tri-Lo-Mili, 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 0.180 or 0.250 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 AUC0-24h 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 AUC0-24h by 19%, NG Cmax by 12% and AUC0-24h by 46%, EE Cmax by 13% and AUC0-24h by 12%. These changes were statistically significant. Increasing age was associated with slight decreases (6% with increasing age by 5 years) in Cmax and AUC0-24h 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-Mili tablets may be explained by any or all of the above demographic parameters.
[See Warnings and Precautions (5.2, 5.11) and Use in Specific Populations (8.1).]
In an active controlled clinical trial lasting 12 months, 1,673 women, 18 to 45 years old completed 11,003 cycles of Tri-Lo-Mili use and a total of 20 pregnancies were reported in Tri-Lo-Mili users. The racial demographic of those treated with Tri-Lo-Mili 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-Mili (norgestimate and ethinyl estradiol tablets USP) are available in a blister pack.
Each blister pack (28 tablets) contains in the following order:
The blister packs are available in the following packages:
Carton of 1 Blister Pack NDC 71205-746-28
See FDA-approved patient labeling (Patient Information and Instruction for Use).
Counsel patients about the following information:
Distributed by:
Aurobindo Pharma USA, Inc.
279 Princeton-Hightstown Road
East Windsor, NJ 08520
Manufactured by:
Aurobindo Pharma Limited
Hyderabad-500 032, India
Relabeled by:
Proficient Rx LP
Thousand Oaks, CA 91320
Revised: 06/2022
Tri-Lo-Mili (trahy-loh-mil-ee)
(norgestimate and ethinyl estradiol tablets USP)
What is the most important information I should know about Tri-Lo-Mili?
Do not use Tri-Lo-Mili 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-Mili?
Tri-Lo-Mili is a birth control pill (oral contraceptive) used by women to prevent pregnancy.
How does Tri-Lo-Mili 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-Mili.
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-Mili?
Do not take Tri-Lo-Mili if you:
If any of these conditions happen while you are taking Tri-Lo-Mili, stop taking Tri-Lo-Mili right away and talk to your healthcare provider. Use non-hormonal contraception when you stop taking Tri-Lo-Mili.
What should I tell my healthcare provider before taking Tri-Lo-Mili?
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-Mili may affect the way other medicines work, and other medicines may affect how well Tri-Lo-Mili 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-Mili?
Read the Instructions for Use at the end of this Patient Information.
What are the possible serious side effects of Tri-Lo-Mili?
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-Mili?
These are not all the possible side effects of Tri-Lo-Mili. 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 Tri-Lo-Mili?
How should I store Tri-Lo-Mili?
General information about the safe and effective use of Tri-Lo-Mili.
Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use Tri-Lo-Mili for a condition for which it was not prescribed. Do not give Tri-Lo-Mili to other people, even if they have the same symptoms that you have.
This Patient Information summarizes the most important information about Tri-Lo-Mili. You can ask your pharmacist or healthcare provider for information about Tri-Lo-Mili that is written for health professionals.
For more information, call Aurobindo Pharma USA, Inc. at 1-866-850-2876.
Does hormonal birth control cause cancer?
It is not known if hormonal birth control pills causes breast cancer. Some studies, but not all, suggest that there could be a slight increase in the risk of breast cancer among current users with longer duration of use.
If you have breast cancer now, or have had it in the past, do not use hormonal birth control 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-Mili?
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-Mili, 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-Mili?
Active ingredients: Each white to off white, pale blue to bluish white, and blue to light blue pill contains norgestimate and ethinyl estradiol.
Inactive ingredients:
White to off white pills: croscarmellose sodium, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, polyethylene glycol, and titanium dioxide.
Pale blue to bluish white pills: croscarmellose sodium, FD&C Blue #2/Indigo carmine aluminum lake, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, polyethylene glycol, and titanium dioxide.
Blue to light blue pills: croscarmellose sodium, FD&C Blue #2/Indigo carmine aluminum lake, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, polyethylene glycol, and titanium dioxide.
Green pills: anhydrous lactose, FD&C Blue No. 2 aluminum lake, ferric oxide yellow, magnesium stearate, microcrystalline cellulose, and povidone.
Tri-Lo-Mili (trahy-loh-mil-ee)
(norgestimate and ethinyl estradiol tablets USP)
Important Information about taking Tri-Lo-Mili
Before you start taking Tri-Lo-Mili:
When should I start taking Tri-Lo-Mili?
If you start taking Tri-Lo-Mili and you have not used a hormonal birth control method before:
If you start taking Tri-Lo-Mili and you are switching from another birth control pill:
If you start taking Tri-Lo-Mili and previously used a vaginal ring or transdermal patch:
If you start taking Tri-Lo-Mili and you are switching from a progestin-only method such as an implant or injection:
If you start taking Tri-Lo-Mili 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-Mili?” above. Follow these instructions for either a Sunday Start or a Day 1 Start.
Sunday 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.
Tri-Lo-Mili comes in Blister Pack.
1. Decide what time of day you want to take your pill.
It is important to take it at about the same time every day.
2. The 28-pill pack has 21 white to off white, pale blue to bluish white, and blue to light blue “active” pills (with hormones) to take for 3 weeks. This is followed by 1 week of green “reminder” pills (without hormones).
3. Also find:
1) where on the pack to start taking pills,
2) in what order to take the pills, and
3) the week numbers as shown in the picture below.
4. Be sure you have ready at all times:
Another kind of birth control (such as condoms or spermicide) to use as a back-up method in case you miss pills.
An extra, full pill pack.
You have a choice of which day to start taking your first pack of pills. Tri-Lo-Mili is available in a blister pack which is preset for a Sunday Start. Day 1 Start stickers are also provided. Decide with your healthcare professional which is the best day for you. Pick a time of day that will be easy to remember.
Sunday Start:
Take the first white to off white “active” pill of the first pack on the Sunday after your period starts, even if you are still bleeding. If your period begins on Sunday, start the pack that same day.
Use another method of birth control (such as condoms or spermicide) as a back-up method if you have sex anytime from the Sunday you start your first pack until the next Sunday (7 days).
Day 1 Start:
Take the first white to off white "active" pill of the first pack during the first 24 hours of your period.
Note: If the first day of your period is a Sunday, you can skip steps #1 and #2.
You will not need to use a back-up method of birth control, since you are starting the pill at the beginning of your period.
What should I do if I miss any Tri-Lo-Mili 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.
This Patient Information and Instructions for Use has been approved by the U.S. Food and Drug Administration.
Distributed by:
Aurobindo Pharma USA, Inc.
279 Princeton-Hightstown Road
East Windsor, NJ 08520
Manufactured by:
Aurobindo Pharma Limited
Hyderabad-500 032, India
Relabeled by:
Proficient Rx LP
Thousand Oaks, CA 91320
Revised: 06/2022
28 day NDC 71205-746-28
Regimen
Tri-Lo-Mili®
(norgestimate and ethinyl
estradiol tablets USP)
0.180 mg/0.025 mg
0.215 mg/0.025 mg
0.250 mg/0.025 mg
This product (like all oral contraceptives) is intended to prevent
pregnancy. It does not protect against HIV infection (AIDS) and other
sexually transmitted diseases.
Rx only 1 Pouch of 28 Tablets
TRI-LO-MILI
norgestimate and ethinyl estradiol kit |
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Labeler - Proficient Rx LP (079196022) |
Establishment | |||
Name | Address | ID/FEI | Business Operations |
---|---|---|---|
Proficient Rx LP | 079196022 | RELABEL(71205-746) |