Norgestimate and Ethinyl Estradiol by is a Prescription medication manufactured, distributed, or labeled by Glenmark Pharmaceuticals Inc., USA, Glenmark Pharmaceuticals Limited. Drug facts, warnings, and ingredients follow.
Norgestimate and ethinyl estradiol tablets are estrogen/progestin COCs, indicated for use by women to prevent pregnancy. (1.1)
Norgestimate and ethinyl estradiol tablets 0.18 mg/0.035 mg, 0.215 mg/0.035 mg, 0.25 mg/0.035 mg are 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.
Norgestimate and ethinyl estradiol tablets 0.18 mg/0.035 mg, 0.215 mg/0.035 mg, 0.25 mg/0.035 mg should be used for the treatment of acne only if the patient desires an oral contraceptive for birth control. (1.2)
Norgestimate and Ethinyl Estradiol Tablets USP, 0.25 mg/0.035 mg, consist of 28 round, flat faced beveled edged, uncoated tablets in the following order (3):
Norgestimate and Ethinyl Estradiol Tablets USP, 0.18 mg/0.035 mg, 0.215 mg/0.035 mg, 0.25 mg/0.035 mg, consist of 28 round, flat faced beveled edged, uncoated tablets in the following order (3):
The most common adverse reactions reported during clinical trials (≥2%) were:
Norgestimate and ethinyl estradiol tablets, 0.25 mg/0.035 mg: headache/migraine, abdominal/gastrointestinal pain, vaginal infection, genital discharge, breast issues (including breast pain, discharge, and enlargement), mood disorders (including depression and mood altered), flatulence, nervousness, rash. (6.1)
Norgestimate and ethinyl estradiol tablets, 0.18 mg/0.035 mg, 0.215 mg/0.035 mg, 0.25 mg/0.035 mg: 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 Glenmark Pharmaceuticals Inc., USA at 1(888)721-7115 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)
Nursing mothers: Not recommended; can decrease milk production. (8.3)
See 17 for PATIENT COUNSELING INFORMATION.
Revised: 6/2019
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, 0.18 mg/0.035 mg, 0.215 mg/0.035 mg, 0.25 mg/0.035 mg and Norgestimate and Ethinyl Estradiol Tablets, 0.25 mg/0.035 mg are indicated for use by females of reproductive potential to prevent pregnancy [see Clinical Studies (14)].
Norgestimate and Ethinyl Estradiol Tablets, 0.18 mg/0.035 mg, 0.215 mg/0.035 mg, 0.25 mg/0.035 mg are 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. Norgestimate and Ethinyl Estradiol Tablets, 0.18 mg/0.035 mg, 0.215 mg/0.035 mg, 0.25 mg/0.035 mg should be used for the treatment of acne only if the patient desires an oral contraceptive for birth control [see Clinical Studies (14)].
Norgestimate and ethinyl estradiol tablets, 0.18 mg/0.035 mg, 0.215 mg/0.035 mg, 0.25 mg/0.035 mg, and norgestimate and ethinyl estradiol tablets, 0.25 mg/0.035 mg are dispensed in blister packs [see How Supplied/Storage and Handling (16)]. Norgestimate and ethinyl estradiol tablets, 0.18 mg/0.035 mg, 0.215 mg/0.035 mg, 0.25 mg/0.035 mg, and norgestimate and ethinyl estradiol tablets, 0.25 mg/0.035 mg 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, 0.25 mg/0.035 mg, or Norgestimate and Ethinyl Estradiol Tablets, 0.18 mg/0.035 mg, 0.215 mg/0.035 mg, 0.25 mg/0.035 mg
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:
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Day 1 Start:
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Sunday Start:
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Switching to Norgestimate and Ethinyl Estradiol Tablets, 0.25 mg/0.035 mg, or Norgestimate and Ethinyl Estradiol Tablets, 0.18 mg/0.035 mg, 0.215 mg/0.035 mg, 0.25 mg/0.035 mg 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, 0.25 mg/0.035 mg, or Norgestimate and Ethinyl Estradiol Tablets, 0.18 mg/0.035 mg, 0.215 mg/0.035 mg, 0.25 mg/0.035 mg |
Start Norgestimate and Ethinyl Estradiol Tablets, 0.25 mg/0.035 mg, or Norgestimate and Ethinyl Estradiol Tablets, 0.18 mg/0.035 mg, 0.215 mg/0.035 mg, 0.25 mg/0.035 mg: |
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Complete instructions to facilitate patient counseling on proper tablet usage are located in the FDA-Approved Patient Labeling.
Starting Norgestimate and Ethinyl Estradiol Tablets, 0.25 mg/0.035 mg, or Norgestimate and Ethinyl Estradiol Tablets, 0.18 mg/0.035 mg, 0.215 mg/0.035 mg, 0.25 mg/0.035 mg after Abortion or Miscarriage
First-trimester
Second-trimester
Starting Norgestimate and Ethinyl Estradiol Tablets, 0.25 mg/0.035 mg, or Norgestimate and Ethinyl Estradiol Tablets, 0.18 mg/0.035 mg, 0.215 mg/0.035 mg, 0.25 mg/0.035 mg after Childbirth
Blister Card Tablet Dispenser
Norgestimate and Ethinyl Estradiol Tablets, 0.25 mg/0.035 mg
Norgestimate and Ethinyl Estradiol Tablets, 0.18 mg/0.035 mg, 0.215 mg/0.035 mg, 0.25 mg/0.035 mg
Norgestimate and Ethinyl Estradiol Tablets, 0.25 mg/0.035 mg:
Norgestimate and Ethinyl Estradiol Tablets, 0.18 mg/0.035 mg, 0.215 mg/0.035 mg, 0.25 mg/0.035 mg
Table 2: Instructions for Missed Norgestimate and Ethinyl Estradiol Tablets, 0.25 mg/0.035 mg, or Norgestimate and Ethinyl Estradiol Tablets, 0.18 mg/0.035 mg, 0.215 mg/0.035 mg, 0.25 mg/0.035 mg
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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. 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 Norgestimate and Ethinyl Estradiol Tablets, 0.18 mg/0.035 mg, 0.215 mg/0.035 mg, 0.25 mg/0.035 mg for acne should follow the guidelines for use of Norgestimate and Ethinyl Estradiol Tablets, 0.18 mg/0.035 mg, 0.215 mg/0.035 mg, 0.25 mg/0.035 mg as an oral contraceptive. Consult the DOSAGE AND ADMINISTRATION section (2.1) for instructions.
Norgestimate and Ethinyl Estradiol Tablets USP, 0.25 mg/0.035 mg are available in blister packs containing 28 tablets, in the following order:
Norgestimate and Ethinyl Estradiol Tablets USP, 0.18 mg/0.035 mg, 0.215 mg/0.035 mg, 0.25 mg/0.035 mg are available in blister cards. Each blister card contains 28 tablets in the following order:
Do not prescribe norgestimate and ethinyl estradiol tablets to women who are known to have 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, 0.25 mg/0.035 mg, and norgestimate and ethinyl estradiol tablets, 0.18 mg/0.035 mg, 0.215 mg/0.035 mg, 0.25 mg/0.035 mg, 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, 0.25 mg/0.035 mg and 231 (4.8%) women discontinued norgestimate and ethinyl estradiol tablets, 0.18 mg/0.035 mg, 0.215 mg/0.035 mg, 0.25 mg/0.035 mg, 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, 0.25 mg/0.035 mg, experienced unscheduled bleeding per cycle in the first year; for norgestimate and ethinyl estradiol tablets, 0.18 mg/0.035 mg, 0.215 mg/0.035 mg, 0.25 mg/0.035 mg, the respective numbers were 13 to 38%. 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.
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.
Norgestimate and Ethinyl Estradiol Tablets, 0.25 mg/0.035 mg
The safety of norgestimate and ethinyl estradiol tablets, 0.25 mg/0.035 mg, 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, 0.25 mg/0.035 mg, 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).
Norgestimate and Ethinyl Estradiol Tablets, 0.18 mg/0.035 mg, 0.215 mg/0.035 mg, 0.25 mg/0.035 mg
The safety of norgestimate and ethinyl estradiol tablets, 0.18 mg/0.035 mg, 0.215 mg/0.035 mg, 0.25 mg/0.035 mg, was evaluated in 4,826 healthy women of child-bearing potential who participated in 6 clinical trials and received at least 1 dose of norgestimate and ethinyl estradiol tablets, 0.18 mg/0.035 mg, 0.215 mg/0.035 mg, 0.25 mg/0.035 mg, 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%).
Serious Adverse Reactions: breast cancer (1 subject), carcinoma of the cervix in situ (1 subject), hypertension (1 subject), and migraine (2 subjects).
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]).
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.
There was no significant difference between norgestimate and ethinyl estradiol tablets, 0.18 mg/0.035 mg, 0.215 mg/0.035 mg, 0.25 mg/0.035 mg, 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.
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 have not been studied in subjects with hepatic impairment. However, steroid hormones may be poorly metabolized in patients with hepatic impairment. Acute or chronic disturbances of liver function may necessitate the discontinuation of COC use until markers of liver function return to normal and COC causation has been excluded. [See Contraindications (4) and Warnings and Precautions (5.2).]
Each of the following products is a combination oral contraceptive containing the progestational compound norgestimate, USP and the estrogenic compound ethinyl estradiol, USP. Norgestimate, USP is designated as (18,19-Dinor-17-pregn-4-en-20-yn-3-one,17-(acetyloxy)-13-ethyl-,oxime,(17α)-(+)-) and ethinyl estradiol, USP is designated as (19-nor-17α-pregna,1,3,5(10)-trien-20-yne-3,17-diol).
Norgestimate and Ethinyl Estradiol Tablets USP, 0.25 mg/0.035 mg
Norgestimate and Ethinyl Estradiol Tablets USP, 0.18 mg/0.035 mg, 0.215 mg/0.035 mg, 0.25 mg/0.035 mg
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).
Table 3: Summary of NGMN, NG and EE pharmacokinetic parameters
Mean (SD) Pharmacokinetic Parameters of Norgestimate and Ethinyl Estradiol Tablets, 0.18 mg/0.035 mg, 0.215 mg/0.035 mg, 0.25 mg/0.035 mg During a Three Cycle Study |
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Analyte |
Cycle |
Day |
Cmax |
tmax (h) |
AUC0-24h |
t1/2 (h) |
NGMN |
3 |
7 |
1.80 (0.46) |
1.42 (0.73) |
15 (3.88) |
NC |
14 |
2.12 (0.56) |
1.21 (0.26) |
16.1 (4.97) |
NC |
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21 |
2.66 (0.47) |
1.29 (0.26) |
21.4 (3.46) |
22.3 (6.54) |
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NG |
3 |
7 |
1.94 (0.82) |
3.15 (4.05) |
34.8 (16.5) |
NC |
14 |
3 (1.04) |
2.21 (2.03) |
55.2 (23.5) |
NC |
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21 |
3.66 (1.15) |
2.58 (2.97) |
69.3 (23.8) |
40.2 (15.4) |
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EE |
3 |
7 |
124 (39.5) |
1.27 (0.26) |
1130 (420) |
NC |
14 |
128 (38.4) |
1.32 (0.25) |
1130 (324) |
NC |
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21 |
126 (34.7) |
1.31 (0.56) |
1090 (359) |
15.9 (4.39) |
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Mean (SD) Pharmacokinetic Parameters of Norgestimate and Ethinyl Estradiol Tablets, 0.25 mg/0.035 mg During a Three Cycle Study |
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Analyte |
Cycle |
Day |
Cmax |
tmax (h) |
AUC0-24h |
t1/2 (h) |
NGMN |
1 |
1 |
1.78 (0.397) |
1.19 (0.25) |
9.90 (3.25) |
18.4 (5.91) |
3 |
21 |
2.19 (0.655) |
1.43 (0.68) |
18.1 (5.53) |
24.9 (9.04) |
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NG |
1 |
1 |
0.649 (0.49) |
1.42 (0.69) |
6.22 (2.46) |
37.8 (14) |
3 |
21 |
2.65 (1.11) |
1.67 (1.32) |
48.2 (20.5) |
45 (20.4) |
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EE |
1 |
1 |
92.2 (24.5) |
1.2 (0.26) |
629 (138) |
10.1 (1.9) |
3 |
21 |
147 (41.5) |
1.13 (0.23) |
1210 (294) |
15 (2.36) |
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=hng/mL
EE: Cmax=pg/mL, AUC0-24h=hpg/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, 0.25 mg/0.035 mg, 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.
In four clinical trials with norgestimate and ethinyl estradiol tablets, 0.18 mg/0.035 mg, 0.215 mg/0.035 mg, 0.25 mg/0.035 mg, 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 to 90% Caucasian, 6 to 10% African-American, with the remainder Asian (≤1%) or Other (2 to 5%). There were no exclusions on the basis of weight; the weight range for women treated was 80 to 310 lbs, with a mean weight of about 132 lbs. The pregnancy rate was approximately 1 pregnancy per 100 women-years.
Norgestimate and ethinyl estradiol tablets, 0.18 mg/0.035 mg, 0.215 mg/0.035 mg, 0.25 mg/0.035 mg, was 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 norgestimate and ethinyl estradiol tablets, 0.18 mg/0.035 mg, 0.215 mg/0.035 mg, 0.25 mg/0.035 mg, 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 norgestimate and ethinyl estradiol tablets, 0.18 mg/0.035 mg, 0.215 mg/0.035 mg, 0.25 mg/0.035 mg, 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 norgestimate and ethinyl estradiol tablets, 0.18 mg/0.035 mg, 0.215 mg/0.035 mg, 0.25 mg/0.035 mg, showed a statistically significant improvement in total lesions compared to those treated with placebo.
Table 4: Acne Vulgaris Indication. Combined Results: Two Multicenter, Placebo-Controlled Trials. Observed Means at Six Months (LOCF)1 and at Baseline. Intent-to-Treat Population
Norgestimate and Ethinyl Estradiol Tablets, 0.18 mg/0.035 mg, 0.215 mg/0.035 mg, 0.25 mg/0.035 mg
(N=221) | Placebo
(N=234) | Difference in Counts between Norgestimate and Ethinyl Estradiol Tablets, 0.18 mg/0.035 mg, 0.215 mg/0.035 mg, 0.25 mg/0.035 mg and Placebo at 6 Months | |||
---|---|---|---|---|---|
# of Lesions | Counts | % Reduction | Counts | % Reduction | |
INFLAMMATORY LESIONS | |||||
Baseline Mean |
19 |
19 | |||
Sixth Month Mean |
10 |
48% |
13 |
30% |
3 (95% CI: -1.2, 5.1) |
NON-INFLAMMATORY LESIONS | |||||
Baseline Mean |
36 |
35 | |||
Sixth Month Mean |
22 |
34% |
25 |
21% |
3 (95% CI: -0.2, 7.8) |
TOTAL LESIONS | |||||
Baseline Mean |
55 |
54 |
7 (95% CI: 2, 11.9) |
||
Sixth Month Mean |
31 |
42% |
38 |
27% |
1 LOCF: Last Observation Carried Forward
Norgestimate and Ethinyl Estradiol Tablets USP, 0.25 mg/0.035 mg are available in blister packs containing 28 tablets, as follows:
NDC: 68462-309-29 1 carton containing 3 blister cards of 28 tablets
Norgestimate and Ethinyl Estradiol Tablets USP, 0.18 mg/0.035 mg, 0.215 mg/0.035 mg, 0.25 mg/0.035 mg are available in blister packs containing 28 tablets, as follows:
NDC: 68462-565-29 1 carton containing 3 blister cards of 28 tablets
See FDA-approved patient labeling (Patient Information and Instructions for Use).
Counsel patients about the following information:
Manufactured by:
Glenmark Pharmaceuticals Ltd.
Colvale-Bardez, Goa 403 513, India
Manufactured for:
Glenmark Pharmaceuticals Inc., USA
Mahwah, NJ 07430
Questions? 1 (888)721-7115
www.glenmarkpharma.com/usa
September 2017
Norgestimate and Ethinyl Estradiol Tablets, 0.25 mg/0.035 mg
[nor eth IN drone/ETH in il ess tra DYE ole]
Norgestimate and Ethinyl Estradiol Tablets, 0.18 mg/0.035 mg, 0.215 mg/0.035 mg, 0.25 mg/0.035 mg
[nor eth IN drone/ETH in il ess 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 tablets, 0.25 mg/0.035 mg and norgestimate and ethinyl estradiol tablets, 0.18 mg/0.035 mg, 0.215 mg/0.035 mg, 0.25 mg/0.035 mg are a birth control pill (oral contraceptive) used by women to prevent pregnancy.
Norgestimate and ethinyl estradiol tablets, 0.18 mg/0.035 mg, 0.215 mg/0.035 mg, 0.25 mg/0.035 mg are 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”). Norgestimate and ethinyl estradiol tablets, 0.18 mg/0.035 mg, 0.215 mg/0.035 mg, 0.25 mg/0.035 mg should only be used to treat acne in women who want to take birth control pills to prevent pregnancy.
How do 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.
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.
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 Glenmark Pharmaceuticals Inc., USA at 1(888)721-7115.
Do birth control pills cause cancer?
Birth control pills do not seem to cause breast cancer. However, if you have breast cancer now, or have had it in the past, do not use birth control pills because some breast cancers are sensitive to hormones. Women who use birth control pills may have a slightly higher chance of getting cervical cancer. However, this may be due to other reasons such as having more sexual partners.
What if I want to become pregnant?
You may stop taking the pill whenever you wish. Consider a visit with your healthcare provider for a pre-pregnancy checkup before you stop taking the pill.
What should I know about my period when taking 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?
Norgestimate and Ethinyl Estradiol Tablets, 0.25 mg/0.035 mg:
Active Ingredient: Each blue pill contains norgestimate and ethinyl estradiol.
Inactive Ingredients:
Blue tablets: lactose monohydrate, povidone, FD&C Blue No. 2, colloidal silicon dioxide, talc, magnesium stearate, and pregelatinized starch.
Light green tablets (inert tablets): D & C Yellow No. 10, FD & C Blue No. 2, lactose monohydrate, magnesium stearate, microcrystalline cellulose, pregelatinized starch and talc.
Norgestimate and Ethinyl Estradiol Tablets, 0.18 mg/0.035 mg, 0.215 mg/0.035 mg, 0.25 mg/0.035 mg.
Active Ingredients: Each white to off white tablet, light blue tablet, and blue tablet contains norgestimate and ethinyl estradiol
Inactive Ingredients:
White to off-white tablets: lactose monohydrate, povidone, magnesium stearate, colloidal silicon dioxide, talc and pregelatinized starch.
Light blue tablets: FD & C Blue No. 2, lactose monohydrate, povidone, magnesium stearate, colloidal silicon dioxide, talc and pregelatinized starch.
Blue tablet: FD & C Blue No. 2, lactose monohydrate, povidone, magnesium stearate, colloidal silicon dioxide, talc and pregelatinized starch.
Light green tablets (inert tablets): D&C Yellow No. 10, FD&C Blue No. 2, lactose monohydrate, magnesium stearate, microcrystalline cellulose, pregelatinized starch and talc.
Instructions For Use
Norgestimate and Ethinyl Estradiol Tablets, 0.25 mg/0.035 mg
[nor eth IN drone/ETH in il ess tra DYE ole]
Norgestimate and Ethinyl Estradiol Tablets, 0.18 mg/0.035 mg, 0.215 mg/0.035 mg, 0.25 mg/0.035 mg
[nor eth IN drone/ETH in il ess 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 a blister card pill dispenser. Read the instructions below for using your blister card pill dispenser.
Instructions for using your blister card pill dispenser:
Norgestimate and Ethinyl Estradiol Tablets, 0.25 mg/0.035 mg
Norgestimate and Ethinyl Estradiol Tablets, 0.18 mg/0.035 mg, 0.215 mg/0.035 mg, 0.25 mg/0.035 mg
Step 1. Starting your pills
Sunday Start: Remove the first pill at the top of the dispenser (Sunday) by pressing the pill through the hole in the bottom of the dispenser. See Figure C.
Day 1 Start:
Step 2. Continue taking 1 pill every day from the blister card as indicated by the arrows and week numbers on the blister card until no pills remain in the first 3 rows of the blister card.
Step 3. The next day take a light green pill from the last row of the blister card. See Figure F.
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.
Manufactured by:
Glenmark Pharmaceuticals Ltd.
Colvale-Bardez, Goa 403 513, India
Manufactured for:
Glenmark Pharmaceuticals Inc., USA
Mahwah, NJ 07430
Questions? 1 (888)721-7115
www.glenmarkpharma.com/usa
This Patient Information and Instructions for Use has been approved by the U.S. Food and Drug Administration.
September 2017
NDC: 68462-565-29
Norgestimate and Ethinyl Estradiol Tablets USP
0.18 mg/0.035 mg, 0.215 mg/0.035 mg, 0.25 mg/0.035 mg
Carton Label
NDC: 68462-565-84
Norgestimate and Ethinyl Estradiol Tablets USP
0.18 mg/0.035 mg, 0.215 mg/0.035 mg, 0.25 mg/0.035 mg
Blister Label
NORGESTIMATE AND ETHINYL ESTRADIOL
norgestimate and ethinyl estradiol kit |
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NORGESTIMATE AND ETHINYL ESTRADIOL
norgestimate and ethinyl estradiol kit |
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Labeler - Glenmark Pharmaceuticals Inc., USA (130597813) |
Establishment | |||
Name | Address | ID/FEI | Business Operations |
---|---|---|---|
Glenmark Pharmaceuticals Limited | 677318665 | ANALYSIS(68462-565, 68462-309) , MANUFACTURE(68462-565, 68462-309) |