TRI-LINYAH- norgestimate and ethinyl estradiol
Northstar Rx LLC
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use Tri-Linyah safely and effectively. See full prescribing information for Tri-Linyah. Tri-Linyah (norgestimate/ethinyl estradiol) tablets, for oral use.
Initial U.S. Approval: 1989
WARNING: CIGARETTE SMOKING and SERIOUS CARDIOVASCULAR EVENTS
See full prescribing information for complete boxed warning.
RECENT MAJOR CHANGES
INDICATIONS AND USAGE
Tri-Linyah is an estrogen/progestin COC, indicated for use by women to prevent pregnancy. (1.1)
Tri-Linyah is also indicated for the treatment of moderate acne vulgaris in females at least 15 years of age, who have no known contraindications to oral contraceptive therapy and have achieved menarche.
Tri-Linyah should be used for the treatment of acne only if the patient desires an oral contraceptive for birth control. (1.2)
DOSAGE AND ADMINISTRATION
DOSAGE FORMS AND STRENGTHS
Tri-Linyah consists of 28 round, biconvex, coated tablets in the following order (3):
WARNINGS AND PRECAUTIONS
The most common adverse reactions reported during clinical trials (≥2%) were:
headache/migraine, breast issues (including breast pain, enlargement, and discharge), vaginal infection, abdominal/gastrointestinal pain, mood disorders (including mood alteration and depression), genital discharge, changes in weight (including weight increased or decreased). (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact Northstar Rx LLC.Toll-Free at 1-800-206-7821 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-Linyah Tablets are indicated for use by females of reproductive potential to prevent pregnancy [see Clinical Studies (14)].
Tri-Linyah is indicated for the treatment of moderate acne vulgaris in females at least 15 years of age, who have no known contraindications to oral contraceptive therapy and have achieved menarche. Tri-Linyah should be used for the treatment of acne only if the patient desires an oral contraceptive for birth control [see Clinical Studies (14)].
Tri-Linyah is dispensed in 28-tablet blister [see How Supplied/Storage and Handling (16)]. Tri-Linyah may be started using either a Day 1 start or a Sunday start (see Table 1). The plastic compact is pre-set for a Sunday start. Day 1 Start day-label stickers are available. 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.
Starting COCs in women not currently using hormonal contraception (Day 1 Start or Sunday Start)
|Day 1 Start:
|Switching to Tri-Linyah 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-Linyah||Start Tri-Linyah:|
|Complete instructions to facilitate patient counseling on proper tablet usage are located in the FDA-Approved Patient Labeling.|
Starting Tri-Linyah after Abortion or Miscarriage
Starting Tri-Linyah after Childbirth
If the patient starts pill-taking on Sunday, the first active pill should be taken on the first Sunday after the patient’s menstrual period begins. Remove the first active pill at the top of the dispenser (Sunday) by pressing the pill through the blister foil.
If the patient will start pill-taking on “Day 1,” place a day-label sticker on the compact which starts with the day of the week the patient will take the first pill. Remove the first active pill at the top of the dispenser (Day 1) by pressing the pill through the blister foil.
||Take the tablet as soon as possible. Continue taking one tablet a day until the pack is finished.|
||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.|
||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].
The timing of initiation of dosing with Tri-Linyah for acne should follow the guidelines for use of Tri-Linyah as an oral contraceptive. Consult the DOSAGE AND ADMINISTRATION section (2.1) for instructions.
Tri-Linyah Tablets are available in blister cards. Each blister card contains 28 tablets in the following order:
Tri-Linyah is contraindicated in females who are known to have or develop the following conditions:
Impaired Liver Function
Do not use Tri-Linyah 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-Linyah if jaundice develops.
Tri-Linyah 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-Linyah prior to starting therapy with the combination drug regimen ombitasvir/paritaprevir/ritonavir, with or without dasabuvir [see Contraindications (4)]. Tri-Linyah can be restarted approximately 2 weeks following completion of treatment with the Hepatitis C combination drug regimen.
Tri-Linyah 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-Linyah 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-Linyah. 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-Linyah develops new headaches that are recurrent, persistent, or severe, evaluate the cause and discontinue Tri-Linyah if indicated.
Consider discontinuation of Tri-Linyah 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 clinical trials of norgestimate and ethinyl estradiol tricycle tablets, the frequency and duration of breakthrough bleeding and/or spotting was assessed in 1,647 patients (21,275 evaluable cycles) and 4,826 patients (35,546 evaluable cycles), respectively. A total of 231 (4.8%) women discontinued norgestimate and ethinyl estradiol tricycle tablets, at least in part, due to bleeding or spotting. Based on data from the clinical trials, 13-38% of women using norgestimate and ethinyl estradiol tricycle tablets experienced unscheduled bleeding per cycle in the first year. The percent of women who experienced breakthrough/unscheduled bleeding tended to decrease over time.
Amenorrhea and Oligomenorrhea
Women who use Tri-Linyah 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-Linyah 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-Linyah if depression recurs to a serious degree.
Tri-Linyah 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)].
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 fi ndings 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.
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-cycle norgestimate and ethinyl estradiol Tablets was evaluated in 4,826 healthy women of child-bearing potential who participated in 6 clinical trials and received at least 1 dose of tri-cycle norgestimate and ethinyl estradiol Tablets for contraception. Two trials were randomized active-controlled trials and 4 were uncontrolled open-label trials. In 3 trials, subjects were followed for up to 24 cycles; in 2 trials, subjects were followed for up to 12 cycles; and in 1 trial, subjects were followed for up to 6 cycles.
Common Adverse Reactions (≥ 2% of subjects): The most common adverse reactions reported by at least 2% of the 4,826 women were the following in order of decreasing incidence: headache/migraine (33.6%), breast issues (including breast pain, enlargement, and discharge) (8.0%), vaginal infection (7.1%), abdominal/gastrointestinal pain (5.6%), mood disorders (including mood alteration and depression) (3.8%), genital discharge (3.2%), and changes in weight (including weight fluctuation, increased or decreased) (2.5%).
Adverse Reactions Leading to Study Discontinuation: Over the trials, between 9 to 27% of subjects discontinued the trial due to an adverse reaction. The most common adverse reactions (≥1%) leading to discontinuation were: metrorrhagia (4.3%), nausea/vomiting (2.8%), headache/migraine (2.4%), mood disorders (including depression and mood altered) (1.1%), and weight increased (1.1%).
Five studies that compared breast cancer risk between ever-users (current or past use) of COCs and never-users of COCs reported no association between ever use of COCs and breast cancer risk, with effect estimates ranging from 0.90 – 1.12 (Figure 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 – 1.33 with current or recent use. Both of these studies found an increased risk of breast cancer with current use of longer duration, with relative risks ranging from 1.03 with less than one year of COC use to approximately 1.4 with more than 8–10 years of COC use.
Figure 1: Relevant Studies of Risk of Breast Cancer with Combined Oral Contraceptives
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 (Incl. 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, venous thrombosis (including Budd Chiari Syndrome and hepatic vein thrombosis);
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-Linyah.
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 hormonal contraceptives include phenytoin, barbiturates, carbamazepine, bosentan, felbamate, griseofulvin, oxcarbazepine, rifampicin, topiramate, rifabutin, rufinamide, aprepitant, and products containing St. John's wort. Interactions between hormonal 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 20–25%. 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-Linyah 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-Linyah Tablets have been established in women of reproductive age. Efficacy is expected to be the same for postpubertal adolescents under the age of 18 and for users 18 years and older. Use of this product before menarche is not indicated.
There was no significant difference between tri-cycle norgestimate and ethinyl estradiol tablets and placebo in mean change in total lumbar spine (L1-L4) and total hip bone mineral density between baseline and Cycle 13 in 123 adolescent females with anorexia nervosa in a double-blind, placebo-controlled, multicenter, one-year treatment duration clinical trial for the Intent To Treat (ITT) population.
Tri-Linyah has not been studied in postmenopausal women and are not indicated in this population.
The pharmacokinetics of Tri-Linyah 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-Linyah 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.
Acne is a skin condition with a multifactorial etiology, including androgen stimulation of sebum production. While the combination of ethinyl estradiol and norgestimate increases sex hormone-binding globulin (SHBG) and decreases free testosterone, the relationship between these changes and a decrease in the severity of facial acne in otherwise healthy women with this skin condition has not been established.
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 norgestimate.
Peak serum concentrations of NGMN and EE are generally reached by 2 hours after administration of Tri-Linyah. Accumulation following multiple dosing of the 250 mcg NGM / 35 mcg EE dose is approximately 2-fold for NGMN and EE compared with single dose administration. The pharmacokinetics of NGMN is dose-proportional following NGM doses of 180 mcg to 250 mcg. Steady-state concentration of EE is achieved by Day 7 of each dosing cycle. Steady-state concentrations of NGMN and NG are achieved by Day 21. Non-linear accumulation (approximately 8 fold) of NG is observed as a result of high-affinity binding to SHBG, which limits its biological activity (Table 3).
|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, NC = not calculated.|
|NGMN and NG: Cmax = ng/mL, AUC0–24h = h∙ng/mL|
|EE: Cmax = pg/mL, AUC0–24h = h∙pg/mL|
|Mean (SD) Pharmacokinetic Parameters of Norgestimate/Ethinyl Estradiol tri-cyclic Tablets(0.18mg/0.035mg,0.215mg/0.035mg,0.25mg/0.035mg)During a Three Cycle Study|
|Analyte||Cycle||Day||Cmax||tmax (h)||AUC0–24h||t1/2 (h)|
|NGMN||3||7||1.80 (0.46)||1.42 (0.73)||15.0 (3.88)||NC|
|14||2.12 (0.56)||1.21 (0.26)||16.1 (4.97)||NC|
|21||2.66 (0.47)||1.29 (0.26)||21.4 (3.46)||22.3 (6.54)|
|NG||3||7||1.94 (0.82)||3.15 (4.05)||34.8 (16.5)||NC|
|14||3.00 (1.04)||2.21 (2.03)||55.2 (23.5)||NC|
|21||3.66 (1.15)||2.58 (2.97)||69.3 (23.8)||40.2 (15.4)|
|EE||3||7||124 (39.5)||1.27 (0.26)||1130 (420)||NC|
|14||128 (38.4)||1.32 (0.25)||1130 (324)||NC|
|21||126 (34.7)||1.31 (0.56)||1090 (359)||15.9 (4.39)|
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.
The metabolites of NGMN and EE are eliminated by renal and fecal pathways. Following administration of 14C-norgestimate, 47% (45–49%) and 37% (16–49%) of the administered radioactivity was eliminated in the urine and feces, respectively. Unchanged NGM was not detected in the urine. In addition to 17-deacetyl norgestimate, a number of metabolites of NGM have been identified in human urine following administration of radiolabeled NGM. These include 18, 19-Dinor-17-pregn-4-en-20-yn-3-one,17-hydroxy-13-ethyl,(17α)-(-);18,19-Dinor-5β-17-pregnan-20-yn,3α,17β-dihydroxy-13-ethyl,(17α), various hydroxylated metabolites and conjugates of these metabolites.
In four clinical trials with tri-cycle norgestimate and ethinyl estradiol tablets, 4,756 women aged 15 to 41 years were studied for 24 cycles, providing a total of 45,244 cycles of exposure. The racial demographic was about 87–90% Caucasian, 6–10% African-American, with the remainder Asian (≤1%) or Other (2–5%). There were no exclusions on the basis of weight; the weight range for women treated was 80–310 lbs, with a mean weight of about 132 lbs. The pregnancy rate was approximately 1 pregnancy per 100 women-years.
Tri-cycle norgestimate and ethinyl estradiol tablets were evaluated for the treatment of acne vulgaris in two randomized, double-blind, placebo-controlled, multicenter, six- (28 day) cycle studies. Two hundred twenty-one patients received tri-cycle norgestimate and ethinyl estradiol tablets and 234 patients received placebo. Mean age at enrollment for both groups was 28 years. At the end of 6 months, the mean total lesion count changed from 55 to 31 (42% reduction) in patients treated with tri-cycle norgestimate and ethinyl estradiol tablets and from 54 to 38 (27% reduction) in patients similarly treated with placebo. Table 4 summarizes the changes in lesion count for each type of lesion. Based on the investigator's global assessment conducted at the final visit, patients treated with tri-cycle norgestimate and ethinyl estradiol tablets showed a statistically significant improvement in total lesions compared to those treated with placebo.
|Norgestimate and ethinyl estradiol tri-cycle tablets|
|Difference in Counts between norgestimate and ethinyl estradiol tri-cycle tablets and Placebo at 6 Months|
|# of Lesions||Counts||% Reduction||Counts||% Reduction|
|Sixth Month Mean||10||48%||13||30%||3 (95% CI: -1.2, 5.1)|
|Sixth Month Mean||22||34%||25||21%||3 (95% CI: -0.2, 7.8)|
|Baseline Mean||55||54||7 (95% CI: 2.0, 11.9)|
|Sixth Month Mean||31||42%||38||27%|
Tri-Linyah Tablets are available in a compact blister card (NDC 16714-363-01).
Each blister card (28 tablets) contains in the following order:
Tri-Linyah is available in the following packaging configurations:
Carton of 1 blister card NDC 16714-363-02
Carton of 3 blister cards NDC 16714-363-03
Carton of 6 blister cards NDC 16714-363-04
Counsel patients about the following information:
Manufactured for: Northstar Rx LLC
Memphis TN 38141
Toll Free 1-800-206-7821
Manufactured by : Novast Laboratories Ltd.
What is the most important information I should know about TRI-LINYAH?
Do not use TRI-LINYAH 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-LINYAH?
TRI-LINYAH is a birth control pill (oral contraceptive) used by women to prevent pregnancy.
TRI-LINYAH is also used to treat moderate acne vulgaris in females 15 years of age and older, who have no known history of allergies or problems taking birth control pills, and have started their menstrual cycle ("period"). TRI-LINYAH should only be used to treat acne in women who want to take birth control pills to prevent pregnancy.
How does TRI-LINYAH 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 out of 100 women may get pregnant during the first year they use TRI-LINYAH.
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-LINYAH?
Do not take TRI-LINYAH if you:
If any of these conditions happen while you are taking TRI-LINYAH, stop taking TRI-LINYAH right away and talk to your healthcare provider. Use non-hormonal contraception when you stop taking TRI-LINYAH.
What should I tell my healthcare provider before taking TRI-LINYAH?
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-LINYAH may affect the way other medicines work, and other medicines may affect how well TRI-LINYAH 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-LINYAH?
Read the Instructions for Use at the end of this Patient Information.
What are the possible serious side effects of TRI-LINYAH?
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-LINYAH?
These are not all the possible side effects of TRI-LINYAH. 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-LINYAH?
How should I store TRI-LINYAH?
General information about the safe and effective use of TRI-LINYAH.
Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use TRI-LINYAH for a condition for which it was not prescribed. Do not give TRI-LINYAH to other people, even if they have the same symptoms that you have.
This Patient Information summarizes the most important information about TRI-LINYAH. You can ask your pharmacist or healthcare provider for information about TRI-LINYAH that is written for health professionals.
For more information, call 1-800-206-7821.
Do birth control pills cause cancer?
It is not known if hormonal birth control pills cause 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-LINYAH?
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-LINYAH, 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-LINYAH?
Active ingredients: Each green, light blue, and blue pill contains norgestimate and ethinyl estradiol.
Green pills: FD&C Blue No.2 Aluminum Lake,FD&C Red No. 40 Aluminum Lake, FD&C Yellow No. 10 Aluminum Lake, titanium dioxide, iron oxide black, iron oxide
yellow, macrogol/ polyethylene glycol 3350 NF, lecithin, talc, polyvinyl alcohol, lactose monohydrate, magnesium stearate and pregelatinized corn starch.
Light Blue pills: FD&C Blue #2 Aluminum Lake,FD&C Red #40 Aluminum Lake, titanium dioxide,iron oxide black, polyvinyl alcohol,
talc, macrogol/polyethylene glycol 3350 NF, lecithin, lactose monohydrate, magnesium stearate and pregelatinized corn starch.
Blue pills: FD&C Blue No. 2 Aluminium Lake,FD&C Blue No. 1 Aluminum lake, FD&C Red No. 40 Aluminum Lake, FD&C Yellow No. 10 Aluminum Lake, titanium dioxide, polyvinyl alcohol,talc, macrogol/PEG 3350 NF, lecithin, lactose monohydrate, magnesium stearate and pregelatinized corn starch.
White pills: titanium dioxide, polydextrose, hypromellose, triacetin, macrogol/polyethylene glycol, lactose monohydrate, magnesium stearate and pregelatinized corn starch.
Important Information about taking TRI-LINYAH
Before you start taking TRI-LINYAH:
When should I start taking TRI-LINYAH?
If you start taking TRI-LINYAH and you have not used a hormonal birth control method before:
If you start taking TRI-LINYAH and you are switching from another birth control pill:
If you start taking TRI-LINYAH and previously used a vaginal ring or transdermal patch:
If you start taking TRI-LINYAH and you are switching from a progestin-only method such as an implant or injection:
If you start taking TRI-LINYAH 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-LINYAH?" above.
TRI-LINYAH is available as a blister card placed within a white compact with the days of the week imprinted on the white compact preset for a Sunday start. The TRI-LINYAH blister card has 21 (7 green,7 light blue and 7 blue) "active" pills (with hormones) to take for 3 weeks. This is followed by 1 week of 7 white "reminder" pills (without hormones). The TRI-LINYAH blister card and the imprinted days of the week on the compact is shown in the picture below.
On the above blister card find where on the card to start taking pills, in what order to take the pills and the week numbers. Day 1 stickers are also provided.
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. Refer to Day 1 Start instructions below.
1. Pick the day label strip that starts with the first day of your period.
2. Place this day label strip over the area on the plastic compact which already has the days of the week (starting with Sunday) imprinted and press firmly. See the picture below as an example.
What should I do if I miss any TRI-LINYAH 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.
Manufactured for: Northstar Rx LLC
Memphis TN 38141
Toll Free 1-800-206-7821
Manufactured by: Novast Laboratories Ltd.
This Patient Information and Instructions for Use has been approved by the U.S. Food and Drug Administration.
Revised: Sep 2022 I0061 Rev.C
norgestimate and ethinyl estradiol kit
|Labeler - Northstar Rx LLC (830546433)|
|Registrant - Novast Laboratories, Ltd. (527695995)|
|Novast Laboratories, Ltd.||527695995||analysis(16714-363) , label(16714-363) , manufacture(16714-363) , pack(16714-363)|