The following Structured Product Label (SPL) was submitted to the FDA by Lupin Pharmaceuticals, Inc. for the product Norgestimate And Ethinyl Estradiol (NDC 68180-840). This document serves as the official prescribing information, containing essential scientific data and clinical materials required for healthcare providers and patients.
This specific version of the label includes detailed information regarding warning: cigarette smoking and serious cardiovascular events, 1.1 oral contraceptive, 2.1 how to start norgestimate and ethinyl estradiol tablets usp, 2.2 how to take norgestimate and ethinyl estradiol tablets usp, 2.3 missed tablets, 2.4 advice in case of gastrointestinal disturbances, 3 dosage forms and strengths, 4 contraindications, and other regulatory disclosures. Use the navigation below to review specific sections of the FDA submission.
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)].
Norgestimate and ethinyl estradiol tablets USP are indicated for use by females of reproductive potential to prevent pregnancy [see CLINICAL STUDIES (14)].
Norgestimate and ethinyl estradiol tablets USP are dispensed in a blister [see HOW SUPPLIED/STORAGE AND HANDLING (16)]. Norgestimate and ethinyl estradiol tablets USP 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 Norgestimate and Ethinyl Estradiol Tablets USP | |
| Starting COCs in women not currently using hormonal contraception (Day 1 Start or Sunday Start) Important: Consider the possibility of ovulation and conception prior to initiation of this product. Tablet Color: ● Norgestimate and ethinyl estradiol tablets USP active tablets are blue (Day 1 to Day 21). ● Norgestimate and ethinyl estradiol tablets USP have green inactive tablets (Day 22 to Day 28). | Day 1 Start: ● Take first active tablet without regard to meals on the first day of menses. ● Take subsequent active tablets once daily at the same time each day for a total of 21 days. ● Take one green inactive tablet daily for 7 days and at the same time of day that active tablets were taken. ● 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) |
| Sunday Start: ● 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 norgestimate and ethinyl estradiol tablets USP. ● Take subsequent active tablets once daily at the same time each day for a total of 21 days. ● Take one green inactive tablet daily for the following 7 days and at the same time of day that active tablets were taken. ● 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 norgestimate and ethinyl estradiol tablets USP 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 norgestimate and ethinyl estradiol tablets USP | Start norgestimate and ethinyl estradiol tablets USP: |
| ● Transdermal patch | ● On the day when next application would have been scheduled |
| ● Vaginal ring | ● On the day when next insertion would have been scheduled |
| ● Injection | ● On the day when next injection would have been scheduled |
| ● Intrauterine contraceptive | ● On the day of removal ● 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. |
| ● Implant | ● On the day of removal |
| Complete instructions to facilitate patient counseling on proper tablet usage are located in the FDA-Approved Patient Labeling. | |
Starting Norgestimate and Ethinyl Estradiol Tablets USP after Abortion or Miscarriage
First-trimester:
Second-trimester:
Starting Norgestimate and Ethinyl Estradiol Tablets USP after Childbirth
Blister Pack:
SET THE DAY
□ Day 1 Start:
□ Sunday Start:
Imgae (4172f029 3c4e 4cc8 Ade0 F96b9d9b7c71 01)
Remove pill "1" by pushing down on the pill. The pill will come out through a hole in the back of the strip.
The patient should wait 24 hours to take the next pill. Continue to take one pill each day until all the pills have been taken.
When your blister is empty, you will start a new blister on the day after pill "28." The first pill in every refill will always be taken on the same day of the week, no matter when the patient's next period starts.
| Table 2: Instructions for Missed Norgestimate and Ethinyl Estradiol Tablets USP | |
| ● 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. |
| ● 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 back-up if the patient has sex within 7 days after missing tablets. |
| ● 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].
Norgestimate and ethinyl estradiol tablets are available in a blister. Each blister contains 28 tablets in the following order:
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 norgestimate and ethinyl estradiol tablets 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 norgestimate and ethinyl estradiol tablets if jaundice develops.
Liver Tumors
Norgestimate and ethinyl estradiol tablets are 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 norgestimate and ethinyl estradiol tablets prior to starting therapy with the combination drug regimen ombitasvir/paritaprevir/ritonavir, with or without dasabuvir [see CONTRAINDICATIONS (4)]. Norgestimate and ethinyl estradiol tablets can be restarted approximately 2 weeks following completion of treatment with the Hepatitis C combination drug regimen.
Norgestimate and ethinyl estradiol tablets are 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 norgestimate and ethinyl estradiol tablets 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 norgestimate and ethinyl estradiol tablets. 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 norgestimate and ethinyl estradiol tablets develops new headaches that are recurrent, persistent, or severe, evaluate the cause and discontinue norgestimate and ethinyl estradiol tablets if indicated.
Consider discontinuation of norgestimate and ethinyl estradiol tablets 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 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 100 (7.5%) women discontinued norgestimate and ethinyl estradiol tablets, at least in part, due to bleeding or spotting. Based on data from the clinical trials, 14 to 34% of women using norgestimate and ethinyl estradiol 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 norgestimate and ethinyl estradiol tablets 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 norgestimate and ethinyl estradiol tablets 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 norgestimate and ethinyl estradiol tablets if depression recurs to a serious degree.
Breast Cancer
Norgestimate and ethinyl estradiol tablets are 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.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.
In women with hereditary angioedema, exogenous estrogens may induce or exacerbate symptoms of angioedema.
Chloasma may occasionally occur, especially in women with a history of chloasma gravidarum. Women with a tendency to chloasma should avoid exposure to the sun or ultraviolet radiation while taking norgestimate and ethinyl estradiol tablets.
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 norgestimate and ethinyl estradiol tablets was evaluated in 1,647 healthy women of child-bearing potential who participated in 3 clinical trials and received at least 1 dose of norgestimate and ethinyl estradiol tablets for contraception. Two trials were randomized active-controlled trials and 1 was an uncontrolled open-label trial. In all 3 trials, subjects were followed for up to 24 cycles.
Common Adverse Reactions (≥ 2% of subjects)
The most common adverse reactions reported by at least 2% of the 1,647 women were the following in order of decreasing incidence: headache/migraine (32.9%), abdominal/gastrointestinal pain (7.8%), vaginal infection (8.4%), genital discharge (6.8%), breast issues (including breast pain, discharge, and enlargement) (6.3%), mood disorders (including depression and mood altered) (5.0%), flatulence (3.2%), nervousness (2.9%), and rash (2.6%).
Adverse Reactions Leading to Study Discontinuation
Over the three trials, between 11 to 21% of subjects discontinued the trial due to an adverse reaction. The most common adverse reactions (≥1%) leading to discontinuation were: metrorrhagia (6.9%), nausea/vomiting (5.0%), headache (4.1%), mood disorders (including depression and mood altered) (2.4%), premenstrual syndrome (1.7%), hypertension (1.4%), breast pain (1.4%), nervousness (1.3%), amenorrhea (1.1%), dysmenorrhea (1.1%), weight increased (1.1%), and flatulence (1.1%).
Serious Adverse Reactions
Breast cancer (1 subject), mood disorders including depression, irritability, and mood swings (1 subject), myocardial infarction (1 subject), and venous thromboembolic events including pulmonary embolism (1 subject) and deep vein thrombosis (DVT) (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 - 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.
Image (4172f029 3c4e 4cc8 Ade0 F96b9d9b7c71 02)
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 (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;
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 norgestimate and ethinyl estradiol tablets.
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 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 norgestimate and ethinyl estradiol 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 norgestimate and ethinyl estradiol 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.
Norgestimate and ethinyl estradiol tablets have not been studied in postmenopausal women and are not indicated in this population.
The pharmacokinetics of norgestimate and ethinyl estradiol tablets 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).]
The pharmacokinetics of norgestimate and ethinyl estradiol tablets has not been studied in women with renal impairment.
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.
Each of the following products 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).
Image (4172f029 3c4e 4cc8 Ade0 F96b9d9b7c71 03)
COCs lower the risk of becoming pregnant primarily by suppressing ovulation. Other possible mechanisms may include cervical mucus changes that inhibit sperm penetration and endometrial changes that reduce the likelihood of implantation.
No specific pharmacodynamic studies were conducted with norgestimate and ethinyl estradiol tablets.
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 norgestimate.
Peak serum concentrations of NGMN and EE are generally reached by 2 hours after administration of norgestimate and ethinyl estradiol tablets. 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).
| Mean (SD) Pharmacokinetic Parameters of Norgestimate and Ethinyl Estradiol Tablets During a Three Cycle Study | ||||||
| Analyte | Cycle | Day | Cmax | tmax (h) | AUC0 to 24h | t1/2 (h) |
| NGMN | 1 | 1 | 1.78 (0.397) | 1.19 (0.250) | 9.90 (3.25) | 18.4 (5.91) |
| 3 | 21 | 2.19 (0.655) | 1.43 (0.680) | 18.1 (5.53) | 24.9 (9.04) | |
| NG | 1 | 1 | 0.649 (0.49) | 1.42 (0.69) | 6.22 (2.46) | 37.8 (14.0) |
| 3 | 21 | 2.65 (1.11) | 1.67 (1.32) | 48.2 (20.5) | 45.0 (20.4) | |
| EE | 1 | 1 | 92.2 (24.5) | 1.2 (0.26) | 629 (138) | 10.1 (1.90) |
| 3 | 21 | 147 (41.5) | 1.13 (0.23) | 1210 (294) | 15.0 (2.36) | |
| Cmax = peak serum concentration, tmax = time to reach peak serum concentration, AUC0 to 24h = area under serum concentration vs time curve from 0 to 24 hours, t1/2 = elimination half-life. NGMN and NG: Cmax = ng/mL, AUC0 to 24h = h•ng/mL EE: Cmax = pg/mL, AUC0 to 24h = h•pg/mL | ||||||
Food Effect:
The effect of food on the pharmacokinetics of norgestimate and ethinyl estradiol tablets 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
The metabolites of NGMN and EE are eliminated by renal and fecal pathways. Following administration of 14C-norgestimate, 47% (45 to 49%) and 37% (16 to 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 three US clinical trials with norgestimate and ethinyl estradiol tablets, 1,651 women aged 18 to 38 years were studied for up to 24 cycles, proving a total of 24,272 cycles of exposure. The racial demographic was about 73 to 86% Caucasian, 8 to 13% African-American, 6 to 14% Hispanic with the remainder Asian or Other (≤1%). There were no exclusions on the basis of weight; the weight range for women treated was 82 to 303 lbs, with a mean weight of about 135 lbs. The pregnancy rate was approximately 1 pregnancy per 100 women-years.
Norgestimate and ethinyl estradiol tablets USP are available in a blister pack (NDC 68180-840-71) containing 28 tablets packed in a pouch (NDC 68180-840-71). Such three pouches are packaged in a carton (NDC 68180-840-73).
Each blister (28 tablets) contains in the following order:
Keep out of reach of children.
See FDA-approved patient labeling (Patient Information and Instructions for Use).
Counsel patients about the following information:
Distributed by:
Lupin Pharmaceuticals, Inc.
Baltimore, Maryland 21202
United States
Manufactured by:
Lupin Limited
Pithampur (M.P.) - 454 775
India
Revised: December 18, 2021
Patient Information
Norgestimate and Ethinyl Estradiol Tablets
(nor JES ti mate and ETH in il es tra DYE ole)
What is the most important information I should know about norgestimate and ethinyl estradiol tablets?
Do not use norgestimate and ethinyl estradiol tablets 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 are norgestimate and ethinyl estradiol tablets?
Norgestimate and ethinyl estradiol tablet is a birth control pill (oral contraceptive) used by women to prevent pregnancy.
How does norgestimate and ethinyl estradiol tablets 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 norgestimate and ethinyl estradiol tablets.
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.
Image (4172f029 3c4e 4cc8 Ade0 F96b9d9b7c71 04)
Who should not take norgestimate and ethinyl estradiol tablets?
Do not take norgestimate and ethinyl estradiol tablets if you:
If any of these conditions happen while you are taking norgestimate and ethinyl estradiol tablets, stop taking norgestimate and ethinyl estradiol tablets right away and talk to your healthcare provider. Use non-hormonal contraception when you stop taking norgestimate and ethinyl estradiol tablets.
What should I tell my healthcare provider before taking norgestimate and ethinyl estradiol tablets?
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.
Norgestimate and ethinyl estradiol tablets may affect the way other medicines work, and other medicines may affect how well norgestimate and ethinyl estradiol tablets work.
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 norgestimate and ethinyl estradiol tablets?
Read the Instructions for Use at the end of this Patient Information.
What are the possible serious side effects of norgestimate and ethinyl estradiol tablets?
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 norgestimate and ethinyl estradiol tablets?
These are not all the possible side effects of norgestimate and ethinyl estradiol tablets. For more information, ask your healthcare provider or pharmacist.
You may report side effects to the FDA at 1-800-FDA-1088 or you may also report side effects to Lupin Pharmaceuticals, Inc. at 1-800-399-2561.
What else should I know about taking norgestimate and ethinyl estradiol tablets?
How should I store norgestimate and ethinyl estradiol tablets?
General information about the safe and effective use of norgestimate and ethinyl estradiol tablets
Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use norgestimate and ethinyl estradiol tablets for a condition for which it was not prescribed. Do not give norgestimate and ethinyl estradiol tablets to other people, even if they have the same symptoms that you have.
This Patient Information summarizes the most important information about norgestimate and ethinyl estradiol tablets. You can ask your pharmacist or healthcare provider for information about norgestimate and ethinyl estradiol tablets 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.
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 norgestimate and ethinyl estradiol tablets?
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 norgestimate and ethinyl estradiol tablets, 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 norgestimate and ethinyl estradiol tablets?
Active ingredients: Each blue pill contains norgestimate and ethinyl estradiol.
Inactive ingredients:
Blue pills: anhydrous lactose, FD & C Blue No. 2 Aluminum Lake, croscarmellose sodium, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, polyethylene glycol, povidone and titanium dioxide.
Green pills: FD & C Blue No. 2 Aluminum Lake, croscarmellose sodium, iron oxide yellow, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, polyethylene glycol and titanium dioxide.
Instructions For Use
Norgestimate and Ethinyl Estradiol Tablets
(nor JES ti mate and ETH in il es tra DYE ole)
Important Information about taking norgestimate and ethinyl estradiol tablets
Before you start taking norgestimate and ethinyl estradiol tablets:
When should I start taking norgestimate and ethinyl estradiol tablets?
If you start taking norgestimate and ethinyl estradiol tablets and you have not used a hormonal birth control method before:
If you start taking norgestimate and ethinyl estradiol tablets and you are switching from another birth control pill:
If you start taking norgestimate and ethinyl estradiol tablets and previously used a vaginal ring or transdermal patch:
If you start taking norgestimate and ethinyl estradiol tablets and you are switching from a progestin-only method such as an implant or injection:
If you start taking norgestimate and ethinyl estradiol tablets 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 norgestimate and ethinyl estradiol tablets?" 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.
Norgestimate and ethinyl estradiol tablets come in blister pack. Read the instructions below for using your blister.
Instructions for using your blister:
Each new blister has 28 pills
Step 1.
SET THE DAY on your BLISTER
Sunday Start:
Each blister has been preprinted with the days of the week, starting with Sunday (Sun), to facilitate a Sunday-Start regimen.
Day 1 Start:
Image (4172f029 3c4e 4cc8 Ade0 F96b9d9b7c71 05)
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 blister is empty, you will start a new blister 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 norgestimate and ethinyl estradiol tablets 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.
Distributed by:
Lupin Pharmaceuticals, Inc.
Baltimore, Maryland 21202
United States
Manufactured by:
Lupin Limited
Pithampur (M.P.) - 454 775
India
This Patient Information and Instructions for Use has been approved by the U.S. Food and Drug Administration.
Revised: December 18, 2021 ID#: 269297
Norgestimate and Ethinyl Estradiol Tablets USP
0.25 mg/0.035 mg
Rx Only
NDC 68180-840-71
Blister Label: 28 Tablets
Image (4172f029 3c4e 4cc8 Ade0 F96b9d9b7c71 06)
Norgestimate and Ethinyl Estradiol Tablets USP
0.25 mg/0.035 mg
Rx Only
NDC 68180-840-71
Pouch Label: 28 Tablets
Image (4172f029 3c4e 4cc8 Ade0 F96b9d9b7c71 07)
Norgestimate and Ethinyl Estradiol Tablets USP
0.25 mg/0.035 mg
Rx Only
NDC 68180-840-73
Carton Label: 3 blisters of 28 Tablets each
Image (4172f029 3c4e 4cc8 Ade0 F96b9d9b7c71 08)
* Please review the disclaimer below.
