Tri-Norinyl Description

TRI-NORINYL® provides a continuous oral contraceptive regimen of 7 blue tablets, 9 yellow-green tablets, 5 more blue tablets, and then 7 orange tablets. Each blue tablet contains norethindrone 0.5 mg and ethinyl estradiol 0.035 mg, each yellow-green tablet contains norethindrone 1 mg and ethinyl estradiol 0.035 mg, and each orange tablet contains inert ingredients.

Norethindrone is a potent progestational agent with the chemical name 17-Hydroxy-19-nor-17α-pregn-4-en-20-yn-3-one. Ethinyl estradiol is an estrogen with the chemical name 19-Nor-17α-pregna-1,3,5 (10)-trien-20-yne-3,17-diol. Their structural formulae follow.

The yellow-green TRI-NORINYL tablets contain the following inactive ingredients: D&C Green No. 5, D&C Yellow No. 10, lactose, magnesium stearate, povidone, and starch.

The blue TRI-NORINYL tablets contain the following inactive ingredients: FD&C Blue No. 1, lactose, magnesium stearate, povidone, and starch.

The inactive orange tablets contain the following inactive ingredients: FD&C Yellow No. 6, lactose, microcrystalline cellulose, and magnesium stearate.

Tri-Norinyl - Clinical Pharmacology

Combination oral contraceptives act by suppression of gonadotrophins. Although the primary mechanism of this action is inhibition of ovulation, other alterations include changes in the cervical mucus (which increase the difficulty of sperm entry into the uterus) and the endometrium (which may reduce the likelihood of implantation).

Indications and Usage for Tri-Norinyl

Oral contraceptives are indicated for the prevention of pregnancy in women who elect to use this product as a method of contraception.

Oral contraceptive products such as Norinyl, which contain 50 mcg of estrogen, should not be used unless medically indicated.

Oral contraceptives are highly effective. Table I lists the typical accidental pregnancy rates for users of combination oral contraceptives and other methods of contraception.1 The efficacy of these contraceptive methods, except sterilization, depends upon the reliability with which they are used. Correct and consistent use of methods can result in lower failure rates.

Contraindications

Oral contraceptives should not be used in women who have the following conditions:

• Thrombophlebitis or thromboembolic disorders
• A past history of deep vein thrombophlebitis or thromboembolic disorders
• Cerebral vascular or coronary artery disease
• Known or suspected carcinoma of the breast
• 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
• Hepatic adenomas, carcinomas or benign liver tumors
• Known or suspected pregnancy
• Are receiving Hepatitis C 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).

Warnings

Precautions

Adverse Reactions/Side Effects

An increased risk of the following serious adverse reactions has been associated with the use of oral contraceptives (see WARNINGS section):

• Thrombophlebitis
• Arterial thromboembolism
• Pulmonary embolism
• Myocardial infarction
• Cerebral hemorrhage
• Cerebral thrombosis
• Hypertension
• Gallbladder disease
• Hepatic adenomas, carcinomas or benign liver tumors

There is evidence of an association between the following conditions and the use of oral contraceptives, although additional confirmatory studies are needed:

• 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
• Rash (allergic)
• 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 the 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
• Budd-Chiari syndrome
• Acne
• Changes in libido
• Colitis

Overdosage

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.

NON-CONTRACEPTIVE HEALTH BENEFITS

The following non-contraceptive health benefits related to the use of oral contraceptives are supported by epidemiological studies which largely utilized oral contraceptive formulations containing estrogen doses exceeding 0.035 mg of ethinyl estradiol or 0.05 mg of mestranol.6-11

Effects on menses:

• Increased menstrual cycle regularity
• Decreased blood loss and decreased incidence of iron deficiency anemia
• Decreased incidence of dysmenorrhea

Effects related to inhibition of ovulation:

• Decreased incidence of functional ovarian cysts
• Decreased incidence of ectopic pregnancies

Effects from long-term use:

• Decreased incidence of fibroadenomas and fibrocystic disease of the breast
• Decreased incidence of acute pelvic inflammatory disease
• Decreased incidence of endometrial cancer
• Decreased incidence of ovarian cancer

Keep this and all medication out of the reach of children.

Tri-Norinyl Dosage and Administration

To achieve maximum contraceptive effectiveness, oral contraceptives must be taken exactly as directed and at intervals not exceeding 24 hours.

For a DAY 1 START, count the first day of menstrual flow as Day 1 and the first blue tablet is then taken on Day 1. For a SUNDAY START when menstrual flow begins on or before Sunday, the first blue tablet is taken on that day. With either a DAY 1 START or SUNDAY START, 1 blue tablet is taken for 7 days, then 1 yellow-green tablet for 9 days, then 1 blue tablet for 5 days, then 1 orange tablet (inert) for 7 days, whether bleeding has stopped or not. With either a DAY 1 START or SUNDAY START 1 tablet is taken each day at the same time for 28 days. After all 28 tablets are taken, whether bleeding has stopped or not, the same dosage schedule is repeated beginning on the following day.

INSTRUCTIONS TO PATIENTS

• To achieve maximum contraceptive effectiveness, the oral contraceptive pill must be taken exactly as directed and at intervals not exceeding 24 hours.
• Important: Women should be instructed to use an additional method of protection until after the first 7 days of administration in the initial cycle.
• Due to the normally increased risk of thromboembolism occurring postpartum, women should be instructed not to initiate treatment with oral contraceptives earlier than 4 weeks after a full-term delivery. If pregnancy is terminated in the first 12 weeks, the patient should be instructed to start oral contraceptives immediately or within 7 days. If pregnancy is terminated after 12 weeks, the patient should be instructed to start oral contraceptives after 2 weeks.33, 77
• If spotting or breakthrough bleeding should occur, the patient should continue the medication according to the schedule. Should spotting or breakthrough bleeding persist, the patient should notify her physician.
• If the patient misses 1 pill, she should be instructed to take it as soon as she remembers and then take the next pill at the regular time. The patient should be advised that missing a pill can cause spotting or light bleeding and that she may be a little sick to her stomach on the days she takes the missed pill with her regularly scheduled pill. If the patient has missed more than one pill, see DETAILED PATIENT LABELING: HOW TO TAKE THE PILL, WHAT TO DO IF YOU MISS PILLS .
• Use of oral contraceptives in the event of a missed menstrual period:
  • If the patient has not adhered to the prescribed dosage regimen, the possibility of pregnancy should be considered after the first missed period and oral contraceptives should be withheld until pregnancy has been ruled out.
  • If the patient has adhered to the prescribed regimen and misses 2 consecutive periods, pregnancy should be ruled out before continuing the contraceptive regimen.

How is Tri-Norinyl supplied

TRI-NORINYL® (norethindrone and ethinyl estradiol tablets USP) is packaged in cartons of three and six tablet dispensers. Each dispenser contains 12 blue active tablets, round in shape debossed with Watson on one side and 254 on the other side; 9 yellow-green active tablets, round in shape debossed with Watson on one side and 259 on the other side; and 7 orange inert tablets, round in shape debossed with Watson on one side and P1 on the other side.

References

1. Hatcher, R.A., Trussell, J. Stewart, F., et al.: Contraceptive Technology: Seventeenth Revised Edition, New York, NY, 1998. 2. Mann, J., et al.: Br Med J 2(5956): 241–245, 1975. 3. Knopp, R.H.: J Reprod Med 31(9): 913–921, 1986. 4. Mann, J.I., et al.: Br Med J 2: 445–447, 1976. 5. Ory, H.: JAMA 237: 2619–2622, 1977. 6. The Cancer and Steroid Hormone Study of the Centers for Disease Control: JAMA 249(2): 1596–1599, 1983. 7. The Cancer and Steroid Hormone Study of the Centers for Disease Control: JAMA 257(6): 796–800, 1987. 8. Ory, H.W.: JAMA 228(1): 68–69, 1974. 9. Ory, H.W., et al.: N Engl J Med 294: 419–422, 1976. 10. Ory, H.W.: Fam Plann Perspect 14: 182–184, 1982. 11. Ory, H.W., et al.: Making Choices, New York, The Alan Guttmacher Institute, 1983. 12. Stadel, B.: N Engl J Med 305(11): 612–618, 1981. 13. Stadel, B.: N Engl J Med 305(12): 672–677, 1981. 14. Adam, S., et al.: Br J Obstet Gynaecol 88: 838–845, 1981. 15. Mann, J., et al.: Br Med J 2(5965): 245–248, 1975. 16. Royal College of General Practitioners' Oral Contraceptive Study: Lancet 1: 541–546, 1981. 17. Slone, D., et al.: N Engl J Med 305(8): 420–424, 1981. 18. Vessey, M.P.: Br J Fam Plann 6 (supplement): 1–12, 1980. 19. Russell-Briefel, R., et al.: Prev Med 15: 352–362, 1986. 20. Goldbaum, G., et al.: JAMA 258(10): 1339–1342, 1987. 21. LaRosa, J.C.: J Reprod Med 31 (9): 906–912, 1986. 22. Krauss, R.M., et al.: Am J Obstet Gynecol 145: 446–452, 1983. 23. Wahl, P., et al.: N Engl J Med 308(15): 862–867, 1983. 24. Wynn, V., et al.: Am J Obstet Gynecol 142(6): 766–771, 1982. 25. Wynn, V., et al.: J Reprod Med 31(9): 892–897, 1986. 26. Inman, W.H., et al.: Br Med J 2(5599): 193–199, 1968. 27. Maguire, M.G., et al.: Am J Epidemiol 110(2): 188–195, 1979. 28. Petitti, D., et al.: JAMA 242(11): 1150–1154, 1979. 29. Vessey, M.P., et al.: Br Med J 2(5599): 199–205, 1968. 30. Vessey, M.P., et al.: Br Med J 2(5658): 651–657, 1969. 31. Porter, J.B., et al.: Obstet Gynecol 59(3): 299–302, 1982. 32. Vessey, M.P., et al.: J Biosoc Sci 8: 373–427, 1976. 33. Mishell, D.R., et al.: Reproductive Endocrinology, Philadelphia, F.A. Davis Co., 1979. 34. Petitti, D.B., et al.: Lancet 2: 234–236, 1978. 35. Collaborative Group for the Study of Stroke in Young Women: JAMA 231(7): 718–722, 1975. 36. Inman, W.H., et al.: Br Med J 2: 203–209, 1970. 37. Meade, T.W., et al.: Br Med J 280(6224): 1157–1161, 1980. 38. Kay, C.R.: Am J Obstet Gynecol 142(6): 762–765, 1982. 39. Gordon, T., et al.: Am J Med 62: 707–714, 1977. 40. Royal College of General Practitioners' Oral Contraception Study: J Coll Gen Pract 33: 75–82, 1983. 41. Ory, H.W.: Fam Plann Perspect 15(2): 57–63, 1983. 42. Paul, C., et al.: Br Med J 293: 723–725, 1986. 43. The Cancer and Steroid Hormone Study of the Centers for Disease Control: N Engl J Med 315(7): 405–411, 1986. 44. Pike, M.C., et al.: Lancet 2: 926–929, 1983. 45. Miller, D.R., et al.: Obstet Gynecol 68: 863–868, 1986. 46. Olsson, H., et al.: Lancet 2: 748–749, 1985. 47. McPherson, K., et al.: Br J Cancer 56: 653–660, 1987. 48. Huggins, G.R., et al.: Fertil Steril 47(5): 733–761, 1987. 49. McPherson, K., et al.: Br Med J 293: 709–710, 1986. 50. Ory, H., et al.: Am J Obstet Gynecol 124(6): 573–577, 1976. 51. Vessey, M.P., et al.: Lancet 2: 930, 1983. 52. Brinton, L.A., et al.: Int J Cancer 38: 339–344, 1986. 53. WHO Collaborative Study of Neoplasia and Steroid Contraceptives: Br Med J 290: 961–965, 1985. 54. Rooks, J.B., et al.: JAMA 242(7): 644–648, 1979. 55. Bein, N.N., et al.: Br J Surg 64: 433–435, 1977. 56. Klatskin, G.: Gastroenterology 73: 386–394, 1977. 57. Henderson, B.E., et al.: Br J Cancer 48: 437–440, 1983. 58. Neuberger, J., et al.: Br Med J 292: 1355–1357, 1986. 59. Forman, D., et al.: Br Med J 292: 1357–1361, 1986. 60. Harlap, S., et al.: Obstet Gynecol 55(4): 447–452, 1980. 61. Savolainen, E., et al.: Am J Obstet Gynecol 140(5): 521–524, 1981. 62. Janerich, D.T., et al.: Am J Epidemiol 112(1): 73–79, 1980. 63. Ferencz, C., et al.: Teratology 21: 225–239, 1980. 64. Rothman, K.J., et al.: Am J Epidemiol 109(4): 433–439, 1979. 65. Boston Collaborative Drug Surveillance Program: Lancet 1: 1399–1404, 1973. 66. Royal College of General Practitioners: Oral contraceptives and health. New York, Pittman, 1974. 67. Rome Group for the Epidemiology and Prevention of Cholelithiasis: Am J Epidemiol 119(5): 796–805, 1984. 68. Strom, B.L., et al.: Clin Pharmacol Ther 39(3): 335–341, 1986. 69. Perlman, J.A., et al.: J Chronic Dis 38(10): 857–864, 1985. 70. Wynn, V., et al.: Lancet 1: 1045–1049, 1979. 71. Wynn, V.: Progesterone and Progestin, New York, Raven Press, 1983. 72. Wynn, V., et al.: Lancet 2: 720–723, 1966. 73. Fisch, I.R., et al.: JAMA 237(23): 2499–2503, 1977. 74. Laragh, J.H.: Am J Obstet Gynecol 126(1): 141–147, 1976. 75. Ramcharan, S., et al.: Pharmacology of Steroid Contraceptive Drugs, New York, Raven Press, 1977. 76. Stockley, I.: Pharm J 216: 140–143, 1976. 77. Dickey, R.P.: Managing Contraceptive Pill Patients, Oklahoma, Creative Informatics Inc., 1984. 78. Porter J.B., Hunter J., Jick H., et al.: Obstet Gynecol 1985; 66: 1–4. 79. Porter J.B., Hershel J., Walker A.M.: Obstet Gynecol 1987; 70: 29–32. 80. Fertility and Maternal Health Drugs Advisory Committee, F.D.A., October, 1989. 81. Schlesselman J., Stadel B.V., Murray P., Lai S.: Breast cancer in relation to early use of oral contraceptives. JAMA 1988; 259: 1828–1833. 82. Hennekens C.H., Speizer F.E., Lipnick R.J., Rosner B., Bain C., Belanger C., Stampfer M.J., Willett W., Peto R.: A case-control study of oral contraceptive use and breast cancer. JNCI 1984; 72: 39–42. 83. Royal College of General Practitioners: Oral contraceptives, venous thrombosis, and varicose veins. J Coll Gen Pract 28: 393–399, 1978. 84. Royal College of General Practitioners' Oral Contraception Study: Effect on Hypertension and benign breast disease of progestogen component in combined oral contraceptives. Lancet 1: 624, 1977.

DETAILED PATIENT LABELING

This product (like all oral contraceptives) is intended to prevent pregnancy. It does not protect against HIV infection (AIDS) and other sexually transmitted diseases.

INTRODUCTION

Any woman who considers using oral contraceptives ("birth control pills" or "the pill") should understand the benefits and risks of using this form of birth control. This leaflet will give you much of the information you will need to make this decision and also will help you determine if you are at risk of developing any of the serious side effects of the pill. It will tell you how to use the pill properly so that it will be as effective as possible. However, this leaflet is not a replacement for a careful discussion between you and your health care provider. You should discuss the information provided in this leaflet with him or her, both when you first start taking the pill and during your regular visits. You also should follow the advice of your health care provider with regard to regular checkups while you are on the pill.

EFFECTIVENESS OF ORAL CONTRACEPTIVES

Oral contraceptives are used to prevent pregnancy and are more effective than other non-surgical methods of birth control. When they are taken correctly, without missing any pills, the chance of becoming pregnant is less than 1% (1 pregnancy per 100 women per year of use). Typical failure rates are actually 3% per year. The chance of becoming pregnant increases with each missed pill during a menstrual cycle.

In comparison, typical failure rates for other nonsurgical methods of birth control during the first year are as follows:

Chance4 85 85 Spermicides5 26 6 40 Periodic abstinence 25 63 Calendar 9 Ovulation method 3 Sympto-thermal6 2 Post-ovulation 1 Withdrawal 19 4 Cap7 Parous women 40 26 42 Nulliparous women 20 9 56 Sponge Parous women 40 20 42 Nulliparous women 20 9 56 Diaphragm 20 6 56 Condom8 Female (Reality) 21 5 56 Male 14 3 61 Pill 5 71 Progestin only 0.5 Combined 0.1 IUD Progesterone T 2.0 1.5 81 Copper T 380A 0.8 0.6 78 LNg 20 0.1 0.1 81 Depo-Provera 0.3 0.3 70 Norplant and Norplant-2 0.05 0.05 88 Female sterilization 0.5 0.5 100 Male sterilization 0.15 0.10 100 Emergency Contraceptive Pills: Treatment initiated within 72 hours after unprotected intercourse reduces the risk of pregnancy by at least 75%.9Lactational Amenorrhea Method: LAM is a highly effective, temporary method of contraception.10

WHO SHOULD NOT TAKE ORAL CONTRACEPTIVES

Some women should not use the pill. For example, you should not take the pill if you are pregnant or think you may be pregnant. You also should not use the pill if you have any of the following conditions:

• A history of heart attack or stroke
• Blood clots in the legs (thrombophlebitis), brain (stroke), lungs (pulmonary embolism) or eyes
• A history of blood clots in the deep veins of your legs
• Chest pain (angina pectoris)
• Known or suspected breast cancer or cancer of the lining of the uterus, cervix or vagina
• Unexplained vaginal bleeding (until a diagnosis is reached by your doctor)
• Yellowing of the whites of the eyes or of the skin (jaundice) during pregnancy or during previous use of the pill
• Liver tumor (benign or cancerous)
• Known or suspected pregnancy
• Take any Hepatitis C drug combination containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir. This may increase levels of the liver enzyme "alanine aminotransferase" (ALT) in the blood.

Tell your health care provider if you have ever had any of these conditions. Your health care provider can recommend a safer method of birth control.

OTHER CONSIDERATIONS BEFORE TAKING ORAL CONTRACEPTIVES

Tell your health care provider if you have or have had:

• Breast nodules, fibrocystic disease of the breast, an abnormal breast x-ray or mammogram
• Diabetes
• Elevated cholesterol or triglycerides
• High blood pressure
• Migraine or other headaches or epilepsy
• Mental depression
• Gallbladder, heart or kidney disease
• History of scanty or irregular menstrual periods

Women with any of these conditions should be checked often by their health care provider if they choose to use oral contraceptives.

Also, be sure to inform your doctor or health care provider if you smoke or are on any medications.

RISKS OF TAKING ORAL CONTRACEPTIVES

1. Risk of developing blood clots

Blood clots and blockage of blood vessels are the most serious side effects of taking oral contraceptives. In particular, a clot in the legs can cause thrombophlebitis and a clot that travels to the lungs can cause a sudden blocking of the vessel carrying blood to the lungs. Rarely, clots occur in the blood vessels of the eye and may cause blindness, double vision, or impaired vision.

If you take oral contraceptives and need elective surgery, need to stay in bed for a prolonged illness or have recently delivered a baby, you may be at risk of developing blood clots. You should consult your doctor about stopping oral contraceptives three to four weeks before surgery and not taking oral contraceptives for two weeks after surgery or during bed rest. You should also not take oral contraceptives soon after delivery of a baby. It is advisable to wait for at least four weeks after delivery if you are not breast feeding. If you are breast feeding, you should wait until you have weaned your child before using the pill (see GENERAL PRECAUTIONS - While breast feeding).

2. Heart attacks and strokes

Oral contraceptives may increase the tendency to develop strokes (stoppage or rupture of blood vessels in the brain) and angina pectoris and heart attacks (blockage of blood vessels in the heart). Any of these conditions can cause death or temporary or permanent disability.

Smoking greatly increases the possibility of suffering heart attacks and strokes. Furthermore, smoking and the use of oral contraceptives greatly increase the chances of developing and dying of heart disease.

3. Gallbladder disease

Oral contraceptive users may have a greater risk than non-users of having gallbladder disease, although this risk may be related to pills containing high doses of estrogen.

4. Liver tumors

In rare cases, oral contraceptives can cause benign but dangerous liver tumors. These benign liver tumors can rupture and cause fatal internal bleeding. In addition, a possible but not definite association has been found with the pill and liver cancers in 2 studies in which a few women who developed these very rare cancers were found to have used oral contraceptives for long periods. However, liver cancers are extremely rare. The chance of developing liver cancer from using the pill is thus even rarer.

5. Cancer of the breast and reproductive organs

There is, at present, no confirmed evidence that oral contraceptives increase the risk of cancer of the reproductive organs in human studies. Several studies have found no overall increase in the risk of developing breast cancer. However, women who use oral contraceptives and have a strong family history of breast cancer or who have breast nodules or abnormal mammograms should be followed closely by their doctors. Some studies have reported an increase in the risk of developing breast cancer, particularly at a younger age. This increased risk appears to be related to duration of use.

Some studies have found an increase in the incidence of cancer of the cervix in women who use oral contraceptives. However, this finding may be related to factors other than the use of oral contraceptives.

ESTIMATED RISK OF DEATH FROM A BIRTH CONTROL METHOD OR PREGNANCY

All methods of birth control and pregnancy are associated with a risk of developing certain diseases which may lead to disability or death. An estimate of the number of deaths associated with different methods of birth control and pregnancy has been calculated and is shown in the following table:

ESTIMATED ANNUAL NUMBER OF BIRTH-RELATED OR METHOD-RELATED DEATHS ASSOCIATED WITH CONTROL OF FERTILITY PER 100,000 NON-STERILE WOMEN, BY FERTILITY CONTROL METHOD ACCORDING TO AGE

Method of control and outcome 15–19 20–24 25–29 30–34 35–39 40–44
Estimates adapted from H.W. Ory 41.

No fertility 7.0 7.4 9.1 14.8 25.7 28.2 control methods* Oral contraceptives 0.3 0.5 0.9 1.9 13.8 31.6 non-smoker** Oral contraceptives 2.2 3.4 6.6 13.5 51.1 117.2 smoker** IUD** 0.8 0.8 1.0 1.0 1.4 1.4 Condom* 1.1 1.6 0.7 0.2 0.3 0.4 Diaphragm/Spermicide* 1.9 1.2 1.2 1.3 2.2 2.8 Periodic abstinence* 2.5 1.6 1.6 1.7 2.9 3.6 * Deaths are birth-related ** Deaths are method-related

In the above table, the risk of death from any birth control method is less than the risk of childbirth except for oral contraceptive users over the age of 35 who smoke and pill users over the age of 40 even if they do not smoke. It can be seen from the table that for women aged 15 to 39 the risk of death is highest with pregnancy (7–26 deaths per 100,000 women, depending on age). Among pill users who do not smoke the risk of death is always lower than that associated with pregnancy for any age group, although over the age of 40 the risk increases to 32 deaths per 100,000 women compared to 28 associated with pregnancy at that age. However, for pill users who smoke and are over the age of 35 the estimated number of deaths exceeds those for other methods of birth control. If a woman is over the age of 40 and smokes, her estimated risk of death is 4 times higher (117/100,000 women) than the estimated risk associated with pregnancy (28/100,000 women) in that age group.

The suggestion that women over 40 who don't smoke should not take oral contraceptives is based on information from older high-dose pills and on less selective use of pills than is practiced today. An Advisory Committee of the FDA discussed this issue in 1989 and recommended that the benefits of oral contraceptive use by healthy, non-smoking women over 40 years of age may outweigh the possible risks. However, all women, especially older women, are cautioned to use the lowest dose pill that is effective.

WARNING SIGNALS

If any of these adverse effects occur while you are taking oral contraceptives, call your doctor immediately:

• Sharp chest pain, coughing of blood or sudden shortness of breath (indicating a possible clot in the lung)
• Pain in the calf (indicating a possible clot in the leg)
• Crushing chest pain or heaviness in the chest (indicating a possible heart attack)
• Sudden severe headache or vomiting, dizziness or fainting, disturbances of vision or speech, weakness or numbness in an arm or leg (indicating a possible stroke)
• Sudden partial or complete loss of vision (indicating a possible clot in the eye)
• Breast lumps (indicating possible breast cancer or fibrocystic disease of the breast: ask your doctor or health care provider to show you how to examine your breasts)
• Severe pain or tenderness in the stomach area (indicating a possible ruptured liver tumor)
• Difficulty in sleeping, weakness, lack of energy, fatigue or change in mood (possibly indicating severe depression)
• Jaundice or a yellowing of the skin or eyeballs, accompanied frequently by fever, fatigue, loss of appetite, dark colored urine or light colored bowel movements (indicating possible liver problems)

SIDE EFFECTS OF ORAL CONTRACEPTIVES

1. Vaginal bleeding

Irregular vaginal bleeding or spotting may occur while you are taking the pill. Irregular bleeding may vary from slight staining between menstrual periods to breakthrough bleeding which is a flow much like a regular period. Irregular bleeding occurs most often during the first few months of oral contraceptive use but may also occur after you have been taking the pill for some time. Such bleeding may be temporary and usually does not indicate any serious problem. It is important to continue taking your pills on schedule. If the bleeding occurs in more than 1 cycle or lasts for more than a few days, talk to your doctor or health care provider.

2. Contact lenses

If you wear contact lenses and notice a change in vision or an inability to wear your lenses, contact your doctor or health care provider.

3. Fluid retention

Oral contraceptives may cause edema (fluid retention) with swelling of the fingers or ankles and may raise your blood pressure. If you experience fluid retention, contact your doctor or health care provider.

4. Melasma (Mask of Pregnancy)

A spotty darkening of the skin is possible, particularly of the face.

5. Other side effects

Other side effects may include change in appetite, headache, nervousness, depression, dizziness, loss of scalp hair, rash and vaginal infections.

If any of these side effects occurs, contact your doctor or health care provider.

GENERAL PRECAUTIONS

1. Missed periods and use of oral contraceptives before or during early pregnancy

At times you may not menstruate regularly after you have completed taking a cycle of pills. If you have taken your pills regularly and miss 1 menstrual period, continue taking your pills for the next cycle but be sure to inform your health care provider before doing so. If you have not taken the pills daily as instructed and miss 1 menstrual period, or if you miss 2 consecutive menstrual periods, you may be pregnant. Check with your health care provider immediately to determine whether you are pregnant. Do not continue to take oral contraceptives until you are sure you are not pregnant, but continue to use another method of birth control.

There is no conclusive evidence that oral contraceptive use is associated with an increase in birth defects when taken inadvertently during early pregnancy. Previously, a few studies had reported that oral contraceptives might be associated with birth defects but these studies have not been confirmed. Nevertheless, oral contraceptives or any other drugs should not be used during pregnancy unless clearly necessary and prescribed by your doctor. You should check with your doctor about risks to your unborn child from any medication taken during pregnancy.

If you are breast feeding, consult your doctor before starting oral contraceptives. Some of the drug will be passed on to the child in the milk. A few adverse effects on the child have been reported, including yellowing of the skin (jaundice) and breast enlargement. In addition, oral contraceptives may decrease the amount and quality of your milk. If possible, do not use oral contraceptives and use another method of contraception while breast feeding. You should consider starting oral contraceptives only after you have weaned your child completely.

3. Laboratory tests

If you are scheduled for any laboratory tests, tell your doctor you are taking birth control pills. Certain blood tests may be affected by birth control pills.

4. Drug interactions

Certain drugs may interact with birth control pills to make them less effective in preventing pregnancy or cause an increase in breakthrough bleeding. Such drugs include rifampin; drugs used for epilepsy such as barbiturates (for example phenobarbital) and phenytoin (Dilantin is one brand of this drug); phenylbutazone (Butazolidin is one brand of this drug) and possibly certain antibiotics. You may need to use additional contraception when you take drugs which can make oral contraceptives less effective.

5. This product (like all oral contraceptives) is intended to prevent pregnancy. It does not protect against transmission of HIV (AIDS) and other sexually transmitted diseases such as chlamydia, genital herpes, genital warts, gonorrhea, hepatitis B, and syphilis.

IMPORTANT POINTS TO REMEMBER

BEFORE YOU START TAKING YOUR PILLS:

1. BE SURE TO READ THESE DIRECTIONS:

   Before you start taking your pills.

   Anytime you are not sure what to do.

2. THE RIGHT WAY TO TAKE THE PILL IS TO TAKE ONE PILL EVERY DAY AT THE SAME TIME.

   If you miss pills you could get pregnant. This includes starting the pack late.

   The more pills you miss, the more likely you are to get pregnant.

3. MANY WOMEN HAVE SPOTTING OR LIGHT BLEEDING, OR MAY FEEL SICK TO THEIR STOMACH DURING THE FIRST 1–3 PACKS OF PILLS.

   If you feel sick to your stomach, do not stop taking the Pill. The problem will usually go away. If it doesn't go away, check with your doctor or clinic.

4. MISSING PILLS CAN ALSO CAUSE SPOTTING OR LIGHT BLEEDING, even when you make up these missed pills.

   On the days you take 2 pills to make up for missed pills, you could also feel a little sick to your stomach.

5. IF YOU HAVE VOMITING OR DIARRHEA, for any reason, or IF YOU TAKE SOME MEDICINES, including some antibiotics, your pills may not work as well.

   Use a back-up method (such as condoms, foam, or sponge) until you check with your doctor or clinic.

6. IF YOU HAVE TROUBLE REMEMBERING TO TAKE THE PILL, talk to your doctor or clinic about how to make pill-taking easier or about using another method of birth control.
7. IF YOU HAVE ANY QUESTIONS OR ARE UNSURE ABOUT THE INFORMATION IN THIS LEAFLET, call your doctor or clinic.

BEFORE YOU START TAKING YOUR PILLS

1. DECIDE WHAT TIME OF DAY YOU WANT TO TAKE YOUR PILL.

   It is important to take it at about the same time every day.

2. LOOK AT YOUR PILL PACK:

   The 28-pill pack has 21 "active" blue and yellow-green pills (with hormones) to take for 3 weeks, followed by 1 week of reminder orange pills (without hormones).

3. ALSO FIND:
   • where on the pack to start taking pills,
   • in what order to take the pills (follow the arrows) and
   • the week numbers as shown in the picture below.

     Active pill colors: blue and yellow-green
     Reminder pill color: orange

   

   * For use of day labels, see WHEN TO START THE FIRST PACK OF PILLS below.

4. BE SURE YOU HAVE READY AT ALL TIMES:

   ANOTHER KIND OF BIRTH CONTROL (such as condoms, foam, or sponge) to use as a back-up in case you miss pills.

   AN EXTRA, FULL PILL PACK.

You have a choice of which day to start taking your first pack of pills. Decide with your doctor or clinic which is the best day for you. Pick a time of day which will be easy to remember.

DAY 1 START:

1. Pick the day label strip that starts with the first day of your period. Place this day label strip over the area that has the days of the week (starting with Sunday) pre-printed on the tablet dispenser.
   Note: if the first day of your period is a Sunday, you can skip step #1.
2. Take the first "active" blue pill of the first pack during the first 24 hours of your period.
3. You will not need to use a back-up method of birth control, since you are starting the pill at the beginning of your period.

SUNDAY START:

1. Take the first "active" blue pill of the first pack on the Sunday after your period starts, even if you are still bleeding. If your period begins on Sunday, start the pack that same day.
2. Use another method of birth control as a back-up method if you have sex anytime from the Sunday you start your first pack until the next Sunday (7 days). Condoms, foam, or the sponge are good back-up methods of birth control.

WHAT TO DO DURING THE MONTH

• TAKE ONE PILL AT THE SAME TIME EVERY DAY UNTIL THE PACK IS EMPTY.

  Do not skip pills even if you are spotting or bleeding between monthly periods or feel sick to your stomach (nausea).

  Do not skip pills even if you do not have sex very often.

• WHEN YOU FINISH A PACK OR SWITCH YOUR BRAND OF PILLS:

  Start the next pack on the day after your last "reminder" pill. Do not wait any days between packs.

If you MISS 1 blue or yellow-green "active" pill:

1. Take it as soon as you remember. Take the next pill at your regular time. This means you may take 2 pills in 1 day.
2. You do not need to use a back-up birth control method if you have sex.

If you MISS 2 blue or yellow-green "active" pills in a row in WEEK 1 OR WEEK 2 of your pack:

1. Take 2 pills on the day you remember and 2 pills the next day.
2. Then take 1 pill a day until you finish the pack.
3. You MAY BECOME PREGNANT if you have sex in the 7 days after you miss pills. You MUST use another birth control method (such as condoms, foam, or sponge) as a back-up for those 7 days.

If you MISS 2 blue or yellow-green "active" pills in a row in THE 3rd WEEK:

1. If you are a Day 1 Starter:

   THROW OUT the rest of the pill pack and start a new pack that same day.

   If you are a Sunday Starter:

   Keep taking 1 pill every day until Sunday.

   On Sunday, THROW OUT the rest of the pack and start a new pack of pills that same day.

2. You may not have your period this month but this is expected. However, if you miss your period 2 months in a row, call your doctor or clinic because you might be pregnant.
3. You MAY BECOME PREGNANT if you have sex in the 7 days after you miss pills. You MUST use another birth control method (such as condoms, foam, or sponge) as a back-up for those 7 days.

If you MISS 3 OR MORE blue or yellow-green "active" pills in a row (during the first 3 weeks):

1. If you are a Day 1 Starter:

   THROW OUT the rest of the pill pack and start a new pack of pills that same day.

   If you are a Sunday Starter:

   Keep taking 1 pill every day until Sunday.

   On Sunday, THROW OUT the rest of the pack and start a new pack of pills that same day.

2. You may not have your period this month but this is expected. However, if you miss your period 2 months in a row, call your doctor or clinic because you might be pregnant.
3. You MAY BECOME PREGNANT if you have sex in the 7 days after you miss pills. You MUST use another birth control method (such as condoms, foam, or sponge) as a back-up for those 7 days.

A REMINDER:
If you forget any of the 7 orange "reminder" pills in Week 4:
THROW AWAY the pills you missed.
Keep taking 1 pill each day until the pack is empty.
You do not need a back-up method.

FINALLY, IF YOU ARE STILL NOT SURE WHAT TO DO ABOUT THE PILLS YOU HAVE MISSED:

Use a BACK-UP METHOD anytime you have sex.

KEEP TAKING ONE "ACTIVE" PILL EACH DAY until you can reach your doctor or clinic.

6. Missed periods, spotting or light bleeding

At times, you may not have a period after you have completed a pack of pills. If you miss 1 period but you have taken the pills exactly as you were supposed to, continue as usual into the next cycle. If you have not taken the pills correctly, and have missed a period, you may be pregnant and you should stop taking the pill until your doctor or clinic determines whether or not you are pregnant. Until you can talk to your doctor or clinic, use an appropriate back-up birth control method. If you miss 2 consecutive periods, you should stop taking the pill until it is determined that you are not pregnant.

Even if spotting or light bleeding should occur, continue taking the pill according to the schedule. Should spotting or light bleeding persist, you should notify your doctor or clinic.

7. Stopping the pill before surgery or prolonged bed rest

If you are scheduled for surgery or you need to stay in bed for a long period of time you should tell your doctor that you are on the pill. You should stop taking the pill four weeks before your operation to avoid an increased risk of blood clots. Talk to your doctor about when you may start taking the pill again.

8. Starting the pill after pregnancy

After you have a baby it is advisable to wait 4-6 weeks before starting to take the pill. Talk to your doctor about when you may start taking the pill after pregnancy.

9. Pregnancy due to pill failure

When the pill is taken correctly, the expected pregnancy rate is approximately 1% (ie, 1 pregnancy per 100 women per year). If pregnancy occurs while taking the pill, there is little risk to the fetus. The typical failure rate of large numbers of pill users is less than 3% when women who have missed pills are included. If you become pregnant, you should discuss your pregnancy with your doctor.

10. Pregnancy after stopping the pill

There may be some delay in becoming pregnant after you stop taking the pill, especially if you had irregular periods before you started using the pill. Your doctor may recommend that you delay becoming pregnant until you have had one or more regular periods.

There does not appear to be any increase in birth defects in newborn babies when pregnancy occurs soon after stopping the pill.

11. Overdosage

There are no reports of serious illness or side effects in young children who have swallowed a large number of pills. In adults, overdosage may cause nausea and/or bleeding in females. In case of overdosage, contact your doctor, clinic or pharmacist.

12. Other information

Your doctor or clinic will take a medical and family history and will examine you before prescribing the pill. The physical examination may be delayed to another time if you request it and the health care provider believes that it is a good medical practice to postpone it. You should be reexamined at least once a year. Be sure to inform your doctor or clinic if there is a family history of any of the conditions listed previously in this leaflet. Be sure to keep all appointments with your doctor or clinic because this is a time to determine if there are early signs of side effects from using the pill.

Do not use the pill for any condition other than the one for which it was prescribed. The pill has been prescribed specifically for you, do not give it to others who may want birth control pills.

If you want more information about birth control pills, ask your doctor or clinic. They have a more technical leaflet called PHYSICIAN LABELING which you might want to read.

NON-CONTRACEPTIVE HEALTH BENEFITS

In addition to preventing pregnancy, use of oral contraceptives may provide certain non-contraceptive health benefits:

• Menstrual cycles may become more regular
• Blood flow during menstruation may be lighter and less iron may be lost. Therefore, anemia due to iron deficiency is less likely to occur
• Pain or other symptoms during menstruation may be encountered less frequently
• Ectopic (tubal) pregnancy may occur less frequently
• Non-cancerous cysts or lumps in the breast may occur less frequently
• Acute pelvic inflammatory disease may occur less frequently
• Oral contraceptive use may provide some protection against developing two forms of cancer: cancer of the ovaries and cancer of the lining of the uterus

Store at 20-25°C (68-77°F). [See USP controlled room temperature.]

Keep this and all medication out of the reach of children.

BRIEF SUMMARY - PATIENT PACKAGE INSERT

This product (like all oral contraceptives) is intended to prevent pregnancy. It does not protect against HIV infection (AIDS) and other sexually transmitted diseases.

Oral contraceptives, also known as "birth control pills" or "the pill", are taken to prevent pregnancy and, when taken correctly, have a failure rate of about 1% per year when used without missing any pills. The typical failure rate of large numbers of pill users is less than 3% per year when women who miss pills are included. For most women, oral contraceptives are also free of serious or unpleasant side effects. However, forgetting to take oral contraceptives considerably increases the chances of pregnancy.

For the majority of women, oral contraceptives can be taken safely, but there are some women who are at high risk of developing certain serious diseases that can be life-threatening or may cause temporary or permanent disability. The risks associated with taking oral contraceptives increase significantly if you:

• Smoke
• Have high blood pressure, diabetes or high cholesterol
• Have or have had clotting disorders, heart attack, stroke, angina pectoris, cancer of the breast or sex organs, jaundice or malignant or benign liver tumors

You should not take the pill if you suspect you are pregnant or have unexplained vaginal bleeding.

Most side effects of the pill are not serious. The most common such effects are nausea, vomiting, bleeding between menstrual periods, weight gain, breast tenderness, and difficulty wearing contact lenses. These side effects, especially nausea and vomiting, may subside within the first 3 months of use.

The serious side effects of the pill occur very infrequently, especially if you are in good health and are young. However, you should know that the following medical conditions have been associated with or made worse by the pill:

1. Blood clots in the legs (thrombophlebitis) or lungs (pulmonary embolism), stoppage or rupture of a blood vessel in the brain (stroke), blockage of blood vessels in the heart (heart attack or angina pectoris), eye or other organs of the body. As mentioned above, smoking increases the risk of heart attacks and strokes and subsequent serious medical consequences.
2. Liver tumors, which may rupture and cause severe bleeding. A possible but not definite association has been found with the pill and liver cancer. However, liver cancers are extremely rare. The chance of developing liver cancer from using the pill is thus even rarer.
3. High blood pressure, although blood pressure usually returns to normal when the pill is stopped.

The symptoms associated with these serious side effects are discussed in the detailed leaflet given to you with your supply of pills. Notify your doctor or health care provider if you notice any unusual physical disturbances while taking the pill. In addition, drugs such as rifampin, as well as some anti-convulsants and some antibiotics, may decrease oral contraceptive effectiveness.

Studies to date of women taking the pill have not shown an increase in the incidence of cancer of the breast or cervix. There is, however, insufficient evidence to rule out the possibility that the pill may cause such cancers. Some studies have reported an increase in the risk of developing breast cancer, particularly at a younger age. This increased risk appears to be related to duration of use.

Taking the pill provides some important non-contraceptive health benefits. These include less painful menstruation, less menstrual blood loss and anemia, fewer pelvic infections and fewer cancers of the ovary and the lining of the uterus.

Be sure to discuss any medical condition you may have with your health care provider. Your health care provider will take a medical and family history before prescribing oral contraceptives and will examine you. The physical examination may be delayed to another time if you request it and the health care provider believes that it is a good medical practice to postpone it. You should be reexamined at least once a year while taking oral contraceptives. The detailed patient information leaflet gives you further information which you should read and discuss with your health care provider.

HOW TO TAKE THE PILL

See full text of HOW TO TAKE THE PILL which is printed in full in the DETAILED PATIENT LABELING .

Call your doctor for medical advice about side effects. You may report side effects to Mayne Pharma at 1-844-825-8500 or to FDA at 1-800-FDA-1088.

Distributed By:
Mayne Pharma
Greenville, NC 27834

Manufactured by:
Patheon, Inc.
Mississauga, Ontario L5N 7K9
CANADA

Content Updated: April 2017

2000007945

PRINCIPAL DISPLAY PANEL - Kit Carton

NDC 51862-470-06

TRI-NORINYL®
(Norethindrone and Ethinyl Estradiol
Tablets USP)

28-DAY REGIMEN
Each blue tablet (12) contains norethindrone 0.5 mg and ethinyl estradiol
0.035 mg; each yellow-green tablet (9) contains norethindrone 1 mg and
ethinyl estradiol 0.035 mg; each orange tablet (7) contains inert ingredients.

6 Tablet Dispensers, 28 Tablets Each

Rx only