Nortrel Drug Information

To achieve maximum contraceptive effectiveness, Nortrel (norethindrone and ethinyl estradiol tablets) must be taken exactly as directed and at intervals not exceeding 24 hours. Nortrel (norethindrone and ethinyl estradiol tablets) is available in the Blister Pack Tablet Dispenser which is preset for a Sunday Start. Day 1 Start is also available. 21-Day Regimen (Sunday Start): When taking Nortrel 1/35 (norethindrone and ethinyl estradiol tablets) Day Regimen, the first "active" tablet should be taken on the first Sunday after menstruation begins.

If the period begins on Sunday, the first "active" tablet should be taken that day. Take one active tablet daily for 21 days. For subsequent cycles, no tablets are taken for 7 days, then a tablet is taken the next day (Sunday). For the first cycle of a Sunday Start regimen, another method of contraception, such as a condom or spermicide, should be used until after the first 7 consecutive days of administration.

If the patient misses one “active” tablet in Weeks 1, 2, or 3, the tablet should be taken as soon as she remembers. If the patient misses two “active” tablets in Week 1 or Week 2, the patient should take two tablets the day she remembers and two tablets the next day; and then continue taking one tablet a day until she finishes the pack. The patient should be instructed to use a back-up method of birth control, such as a condom or spermicide, if she has sex in the seven days after missing pills.

If the patient misses two “active” tablets in the third week or misses three or more “active” tablets in a row, the patient should continue taking one tablet every day until Sunday. On Sunday the patient should throw out the rest of the pack and start a new pack that same day. The patient should be instructed to use a back-up method of birth control if she has sex in the seven days after missing pills.

Complete instructions to facilitate patient counseling on proper pill usage may be found in the Detailed Patient Labeling (“How to Take the Pill" section). 21-Day Regimen (Day 1 Start): The dosage of Nortrel 1/35 (norethindrone and ethinyl estradiol tablets) Day Regimen, for the initial cycle of therapy is one “active” tablet administered daily from the 1st day through the 21st day of the menstrual cycle, counting the first day of menstrual flow as “Day 1.” For subsequent cycles, no tablets are taken for 7 days, then a new course is started of one tablet a day for 21 days. The dosage regimen then continues with 7 days of no medication, followed by 21 days of medication, instituting a three-weeks-on, one-week-off dosage regimen. If the patient misses one “active” tablet in Weeks 1, 2, or 3, the tablet should be taken as soon as she remembers.

If the patient misses two “active” tablets in Week 1 or Week 2, the patient should take two tablets the day she remembers and two tablets the next day; and then continue taking one tablet a day until she finishes the pack. The patient should be instructed to use a back-up method of birth control, such as a condom or spermicide, if she has sex in the seven days after missing pills. If the patient misses two “active” tablets in the third week or misses three or more “active” tablets in a row, the patient should throw out the rest of the pack and start a new pack that same day.

The patient should be instructed to use a back-up method of birth control if she has sex in the seven days after missing pills. Complete instructions to facilitate patient counseling on proper pill usage may be found in the Detailed Patient Labeling (“How to Take the Pill" section). 28-Day Regimen (Sunday Start): When taking Nortrel 1/35 and 0.5/35 (norethindrone and ethinyl estradiol tablets) Day Regimen, the first “active” tablet should be taken on the first Sunday after menstruation begins. If the period begins on Sunday, the first “active” tablet should be taken that day.

Take one active tablet daily for 21 days followed by one white “reminder” tablet daily for 7 days. After 28 tablets have been taken, a new course is started the next day (Sunday). For the first cycle of a Sunday Start regimen, another method of contraception such as a condom or spermicide should be used until after the first 7 consecutive days of administration. If the patient misses one “active” tablet in Weeks 1, 2, or 3, the tablet should be taken as soon as she remembers.

If the patient misses two “active” tablets in Week 1 or Week 2, the patient should take two tablets the day she remembers and two tablets the next day; and then continue taking one tablet a day until she finishes the pack. The patient should be instructed to use a back-up method of birth control such as a condom or spermicide if she has sex in the seven days after missing pills. If the patient misses two “active” tablets in the third week or misses three or more “active” tablets in a row, the patient should continue taking one tablet every day until Sunday.

On Sunday the patient should throw out the rest of the pack and start a new pack that same day. The patient should be instructed to use a back-up method of birth control if she has sex in the seven days after missing pills. Complete instructions to facilitate patient counseling on proper pill usage may be found in the Detailed Patient Labeling (“How to Take the Pill" section). 28-Day Regimen (Day 1 Start): The dosage of Nortrel 1/35 and 0.5/35 (norethindrone and ethinyl estradiol tablets) Day Regimen, for the initial cycle of therapy is one “active” tablet administered daily from the 1st through the 21st day of the menstrual cycle, counting the first day of menstrual flow as “Day 1” followed by one white “reminder” tablet daily for 7 days.

Tablets are taken without interruption for 28 days. After 28 tablets have been taken, a new course is started the next day. If the patient misses one “active” tablet in Weeks 1, 2, or 3, the tablet should be taken as soon as she remembers.

If the patient misses two “active” tablets in Week 1 or Week 2, the patient should take two tablets the day she remembers and two tablets the next day; and then continue taking one tablet a day until she finishes the pack. The patient should be instructed to use a back-up method of birth control such as a condom or spermicide if she has sex in the seven days after missing pills. If the patient misses two “active” tablets in the third week or misses three or more “active” tablets in a row, the patient should throw out the rest of the pack and start a new pack that same day.

The patient should be instructed to use a back-up method of birth control if she has sex in the seven days after missing pills. Complete instructions to facilitate patient counseling on proper pill usage may be found in the Detailed Patient Labeling (“How to Take the Pill" section). The use of Nortrel 1/35 and 0.5/35 (norethindrone and ethinyl estradiol tablets) for contraception may be initiated 4 weeks postpartum in women who elect not to breastfeed. When the tablets are administered during the postpartum period, the increased risk of thromboembolic disease associated with the postpartum period must be considered. (See CONTRAINDICATIONS and WARNINGS concerning thromboembolic disease.

See also PRECAUTIONS, Nursing Mothers.) The possibility of ovulation and conception prior to initiation of medication should be considered. (See Discussion of Dose-Related Risk of Vascular Disease from Oral Contraceptives.)

• Post Marketing Experience: 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 2). Three studies compared breast cancer risk between current or recent COC users (<6 months since last use) and never users of COCs (Figure 2). 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 2: 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. An increased risk of the following serious adverse reactions has been associated with the use of oral contraceptives (see WARNINGS ). Thrombophlebitis and venous thrombosis with or without embolism Arterial thromboembolism Pulmonary embolism Myocardial infarction Cerebral hemorrhage Cerebral thrombosis Hypertension Gallbladder disease Hepatic adenomas or benign liver tumors There is evidence of an association between the following conditions and the use of oral contraceptives: Mesenteric thrombosis Retinal thrombosis The following adverse reactions have been reported in patients receiving oral contraceptives and are believed to be drug-related: Nausea Vomiting Gastrointestinal symptoms (such as abdominal cramps and bloating) Breakthrough bleeding Spotting Change in menstrual flow Amenorrhea Temporary infertility after discontinuation of treatment Edema Melasma which may persist Breast changes: tenderness, enlargement, secretion Change in weight (increase or decrease) Change in cervical erosion and secretion Diminution in lactation when given immediately postpartum Cholestatic jaundice Migraine Allergic reaction, including rash, urticaria, angioedema Mental depression Reduced tolerance to carbohydrates Vaginal candidiasis Change in corneal curvature (steepening) Intolerance to contact lenses The following adverse reactions have been reported in users of oral contraceptives and a causal association has been neither confirmed nor refuted: Pre-menstrual syndrome Cataracts Changes in appetite Cystitis-like syndrome Headache Nervousness Dizziness Hirsutism Loss of scalp hair Erythema multiforme Erythema nodosum Hemorrhagic eruption Vaginitis Porphyria Impaired renal function Hemolytic uremic syndrome Acne Changes in libido Colitis Budd-Chiari Syndrome The following adverse reactions were also reported in clinical trials or during post-marketing experience: Gastrointestinal Disorders: diarrhea, pancreatitis; Musculoskeletal and Connective Tissue Disorders: muscle spasms, back pain; Reproductive System and Breast Disorders vulvovaginal pruritus, pelvic pain, dysmenorrhea, vulvovaginal dryness; Psychiatric Disorders: anxiety, mood swings, mood altered; Skin and Subcutaneous Tissue Disorders: pruritus, photosensitivity reaction; General Disorders and Administration Site Conditions: edema peripheral, fatigue, irritability, asthenia, malaise; Neoplasms Benign, Malignant, and Unspecified (Including Cysts and Polyps): breast cancer, breast mass, breast neoplasm, cervix carcinoma; Immune System Disorders: anaphylactic/anaphylactoid reaction ; Hepatobiliary Disorders: hepatitis, cholelithiasis. Figure 2

8. Drug Interactions Consult the labeling of concurrently-used drugs to obtain further information about interactions with hormonal contraceptives or the potential for enzyme alterations. Effects of Other Drugs on Combined Hormonal Contraceptives Substances decreasing the plasma concentrations of COCs and potentially diminishing the efficacy 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 CHCs 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 CHCs, and to continue back-up contraception for 28 days after discontinuing the enzyme inducer to ensure contraceptive reliability.

Substances increasing the plasma concentrations of COCs Co-administration of atorvastatin or rosuvastatin and certain COCs containing EE increase AUC values for EE by approximately 20-25%. 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 or increase ) /HCV protease inhibitors (decrease ) or with non-nucleoside reverse transcriptase inhibitors (decrease or increase ). Concomitant Use with HCV Combination Therapy – Liver Enzyme Elevation Do not co-administer Nortrel with HCV drug combinations containing ombitasvir/ paritaprevir/ritonavir, with or without dasabuvir, due to potential for ALT elevations (see WARNINGS, Risk of Liver Enzyme Elevations with Concomitant Hepatitis C Treatment ). Colesevelam : Colesevelam, a bile acid sequestrant, given together with a combination oral hormonal contraceptive, has been shown to significantly decrease the AUC of EE. A drug interaction between the contraceptive and colesevelam was decreased when the two drug products were given 4 hours apart.

Effects of Combined Hormonal Contraceptives on Other Drugs COCs containing EE may inhibit the metabolism of other compounds (e.g., cyclosporine, prednisolone, theophylline, tizanidine, and voriconazole) and increase their plasma concentrations. COCs have been shown to decrease plasma concentrations of acetaminophen, clofibric acid, morphine, salicylic acid, temazepam and lamotrigine. Significant decrease in plasma concentration of lamotrigine has been shown, likely due to induction of lamotrigine glucuronidation.

This may reduce seizure control; therefore, dosage adjustments of lamotrigine may be necessary. Women on thyroid hormone replacement therapy may need increased doses of thyroid hormone because serum concentrations of thyroid-binding globulin increases with use of COCs.

11. Pregnancy Pregnancy Category X. See CONTRAINDICATIONS and WARNINGS.

13. Pediatric Use Safety and efficacy of Nortrel 0.5/35 and 1/35 have been established in women of reproductive age. Safety and efficacy are expected to be the same for postpubertal adolescents under the age of 16 and for users 16 years and older. Use of this product before menarche is not indicated. 14. Geriatric Use This product has not been studied in women over 65 years of age and is not indicated in this population.

Nortrel 0.5/35 and 1/35 is contraindicated in females who are known to have or develop the following conditions: Thrombophlebitis or thromboembolic disorders A past history of deep vein thrombophlebitis or thromboembolic disorders Known thrombophilic conditions Cerebral vascular or coronary artery disease (current or history) Valvular heart disease with complications Persistent blood pressure values of > 160 mm Hg systolic or > 100 mg Hg diastolic 96 Diabetes with vascular involvement Headaches with focal neurological symptoms Major surgery with prolonged immobilization Current diagnosis of, or history of, breast cancer, which may be hormone-sensitive Carcinoma of the endometrium or other known or suspected estrogen-dependent neoplasia Undiagnosed abnormal genital bleeding Cholestatic jaundice of pregnancy or jaundice with prior pill use Acute or chronic hepatocellular disease with abnormal liver function Hepatic adenomas or carcinomas Known or suspected pregnancy Hypersensitivity to any component of this product Are receiving Hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, due to the potential for ALT elevations (see WARNINGS, Risk of Liver Enzyme Elevations with Concomitant Hepatitis C Treatment ).

Serious ill effects have not been reported following acute ingestion of large doses of oral contraceptives by young children. Overdosage may cause nausea, and withdrawal bleeding may occur in females.