Norinyl (Norethindrone / Mestranol)

NORINYL® 1/50

Searle

Norethindrone – Mestranol

Oral Contraceptive

Action And Clinical Pharmacology: Estrogen-progestogen combinations act primarily through the mechanism of gonadotropin suppression due to the estrogenic and progestational activity of their components. Although the primary mechanism of action is inhibition of ovulation, alterations in the cervical mucus and the endometrium may also contribute to effectiveness.

Indications And Clinical Uses: Prevention of pregnancy.

Contra-Indications: History of or actual thrombophlebitis or thromboembolic disorders; history of or actual cerebrovascular disorders; history of or actual myocardial infarction or coronary arterial disease; active liver disease or history of or actual benign or malignant liver tumors; history of or known or suspected carcinoma of the breast; history of or known or suspected estrogen-dependent neoplasia; undiagnosed abnormal vaginal bleeding; any ocular lesion arising from ophthalmic vascular disease, such as partial or complete loss of vision or defect in visual fields; when pregnancy is suspected or diagnosed.

Manufacturers’ Warnings In Clinical States: Predisposing Factors for Coronary Artery Disease: Cigarette smoking increases the risk of serious cardiovascular side effects and mortality. Birth control pills increase this risk, especially with increasing age. Convincing data are available to support an upper age limit of 35 years for oral contraceptive use in women who smoke.

Other women who are independently at high risk for cardiovascular disease include those with diabetes, hypertension, abnormal lipid profile, or a family history of these. Whether oral contraceptives accentuate this risk is unclear.

In low risk, nonsmoking women of any age, the benefits of oral contraceptive use outweigh the possible cardiovascular risks associated with low-dose formulations. Consequently, oral contraceptives may be prescribed for these women up to the age of menopause.

Cigarette smoking increases the risk of serious adverse effects on the heart and blood vessels. This risk increases with age and becomes significant in oral contraceptive users over 35 years of age. Women should be counselled not to smoke.

Discontinue Medication at the Earliest Manifestation of the Following:

A. Thromboembolic and cardiovascular disorders such as: thrombophlebitis, pulmonary embolism, cerebrovascular disorders, myocardial ischemia, mesenteric thrombosis and retinal thrombosis.

B. Conditions that predispose to venous stasis and to vascular thrombosis, e.g., immobilization after accidents or confinement to bed during long-term illness. Other nonhormonal methods of contraception should be used until regular activities are resumed. For use of oral contraceptives when surgery is contemplated, see Precautions.

C. Visual defects, partial or complete.

D. Papilledema or ophthalmic vascular lesions.

E. Severe headache of unknown etiology or worsening of pre-existing migraine headache.

Precautions: Physical Examination and Followup: Before oral contraceptives are used, a thorough history and physical examination should be performed, including a blood pressure determination. Breasts, liver, extremities and pelvic organs should be examined and a Papanicolaou smear should be taken if the patient has been sexually active.

The first followup visit should be done 3 months after oral contraceptives are prescribed. Thereafter, examinations should be performed at least once a year or more frequently if indicated. At each annual visit, examination should include those procedures that were done at the initial visit as outlined above or per recommendations of the Canadian Workshop on Screening for Cancer of the Cervix. Their suggestion was that, for women who had 2 consecutive negative Pap smears, screening could be continued every 3 years up to the age of 69.

Pregnancy: Fetal abnormalities have been reported to occur in the offspring of women who have taken estrogen-progestogen combinations in early pregnancy. Rule out pregnancy as soon as it is suspected.

Lactation: The use of oral contraceptives during the period a mother is breast-feeding her infant may not be advisable. The hormonal components are excreted in breast milk and may reduce its quantity and quality. The long-term effects on the developing child are not known.

Hepatic Function: Patients who have had jaundice including a history of cholestatic jaundice during pregnancy should be given oral contraceptives with great care and under close observation.

The development of severe generalized pruritus or icterus requires that the medication be withdrawn until the problem is resolved.

If a patient develops jaundice that proves to be cholestatic in type, the use of oral contraceptives should not be resumed. In patients taking oral contraceptives, changes in the composition of the bile may occur and an increased incidence of gallstones has been reported.

Hepatic nodules have been reported to be associated with use of oral contraceptives, particularly in long-term users of oral contraceptives. These nodules include benign hepatic adenomas, focal nodular hyperplasia and other hepatic lesions. In addition, hepatocellular carcinoma has been reported. Although these lesions are extremely rare, they have caused fatal intra-abdominal hemorrhage and should be considered in women presenting with an abdominal mass, acute abdominal pain, or evidence of intra-abdominal bleeding.

Hypertension: Patients with essential hypertension whose blood pressure is well-controlled may be given oral contraceptives but only under close supervision. If a significant elevation of blood pressure in previously normotensive or hypertensive subjects occurs at any time during the administration of the drug, cessation of medication is necessary.

Migraine and Headache: The onset or exacerbation of migraine or the development of headache of a new pattern which is recurrent, persistent or severe, requires discontinuation of oral contraceptives and evaluation of the cause.

Diabetes: Current low dose oral contraceptives exert minimal impact on glucose metabolism. Diabetic patients, or those with a family history of diabetes, should be observed closely to detect any worsening of carbohydrate metabolism. Patients predisposed to diabetes who can be kept under close supervision may be given oral contraceptives. Young diabetic patients whose disease is of recent origin, well-controlled, and not associated with hypertension or other signs of vascular disease such as ocular fundal changes should be monitored more frequently while using oral contraceptives.

Ocular Disorders: Patients who are pregnant or are taking oral contraceptives may experience corneal edema that may cause visual disturbances and changes in tolerance to contact lenses, especially of the rigid type. Soft contact lenses usually do not cause disturbances. If visual changes or alterations in tolerance to contact lenses occur, temporary or permanent cessation of wear may be advised.

Breasts: Increasing age and a strong family history are the most significant risk factors for the development of breast cancer. Other established risk factors include obesity, nulliparity and late age at first full-term pregnancy. The identified groups of women that may be at increased risk of developing breast cancer before menopause are long-term users of oral contraceptives (more than 8 years) and starters at early age. In a few women, the use of oral contraceptives may accelerate the growth of an existing but undiagnosed breast cancer. Since any potential increased risk related to oral contraceptive use is small, there is no reason to change prescribing habits at present.

Women receiving oral contraceptives should be instructed in self-examination of their breasts. Their physicians should be notified whenever any masses are detected. A yearly clinical breast examination is also recommended because, if a breast cancer should develop, drugs that contain estrogen may cause a rapid progression.

Vaginal Bleeding: Persistent irregular vaginal bleeding requires assessment to exclude underlying pathology.

Fibroids: Patients with fibroids (leiomyomata) should be carefully observed. Sudden enlargement, pain, or tenderness requires discontinuance of the use of oral contraceptives.

Emotional Disorders: Patients with a history of emotional disturbances, especially the depressive type, may be more prone to have a recurrence of depression while taking oral contraceptives. In cases of a serious recurrence, a trial of an alternate method of contraception should be made which may help to clarify the possible relationship. Women with premenstrual syndrome (PMS) may have a varied response to oral contraceptives, ranging from symptomatic improvement to worsening of the condition.

Metabolic and Endocrine Diseases: In metabolic or endocrine diseases and when metabolism of calcium and phosphorus is abnormal, careful clinical evaluation should precede medication and a regular followup is recommended.

Connective Tissue Disease: The use of oral contraceptives in some women has been associated with positive lupus erythematous cell tests and with clinical lupus erythematous. In some instances, exacerbation of rheumatoid arthritis and synovitis have been observed.

Laboratory Tests: Results of laboratory tests should be interpreted in the light of the fact that the patient is on oral contraceptives. The laboratory tests listed below are modified.

A. Liver function tests: Aspartate serum transaminase (AST): variously reported elevations. Alkaline phosphatase and gamma glutamine transaminase (GGT): slightly elevated.

B. Coagulation tests: Minimal elevation of test values reported for such parameters as Factors VII, VIII, IX and X. Increased platelet aggregation. Decreased antithrombin III.

C. Thyroid function tests: Protein binding of thyroxine is increased as indicated by increased total serum thyroxine concentrations and decreased T3 resin uptake.

D. Lipoproteins: Small changes of unproven clinical significance may occur in lipoprotein cholesterol fractions.

E. Gonadotropins: LH and FSH levels are suppressed by the use of oral contraceptives. Wait 2 weeks after discontinuing the use of oral contraceptives before measurements are made.

Tissue Specimens: Pathologists should be advised of oral contraceptive therapy when specimens obtained from surgical procedures and Pap smears are submitted for examination.

Return to Fertility: After discontinuing oral contraceptive therapy, the patient should delay pregnancy until at least 1 normal spontaneous cycle has occurred in order to date the pregnancy. An alternative contraceptive method should be used during this time.

Amenorrhea: Women having a history of oligomenorrhea, secondary amenorrhea, or irregular cycles may remain anovulatory or become amenorrheic following discontinuation of estrogen-progestin combination therapy.

Amenorrhea, especially if associated with breast secretion, that continues for 6 months or more after withdrawal, warrants a careful assessment of hypothalamic-pituitary function.

Thromboembolic Complications – Postsurgery: There is an increased risk of postsurgery thromboembolic complications in oral contraceptive users, after major surgery. If feasible, oral contraceptives should be discontinued and an alternative method substituted at least 1 month prior to major elective surgery. Oral contraceptives should not be resumed until the first menstrual period after hospital discharge following surgery.

Drug Interactions: The concurrent administration of oral contraceptives with other drugs may result in an altered response to either agent. Reduced effectiveness of the oral contraceptive, should it occur, is more likely with the low dose formulations. It is important to ascertain all drugs that a patient is taking, both prescription and nonprescription, before oral contraceptives are prescribed.

Refer to the revised 1994 Report on Oral Contraceptives, Health Canada, for possible drug interactions with oral contraceptives.

Noncontraceptive Benefits of Oral Contraceptives: Several health advantages other than contraception have been reported.

Effects on menses: Increased menstrual cycle regularity; decreased menstrual blood loss; decreased incidence of iron deficiency anemia secondary to reduced menstrual blood loss; decreased incidence of dysmenorrhea.

Effects related to ovulation inhibition: Decreased incidence of functional ovarian cysts; decreased incidence of ectopic pregnancy.

Effects on other organs of the reproductive tract: Decreased incidence of acute salpingitis; decreased incidence of endometrial cancer (50%); decreased incidence of ovarian cancer (40%); potential beneficial effects on endometriosis; improvement of acne vulgaris, hirsutism, and other androgen-mediated disorders.

Effects on breasts: Decreased incidence of benign breast disease (fibroadenomas and fibrocystic breast disease); decreased incidence of breast biopsies.

The noncontraceptive benefits of oral contraceptives should be considered in addition to the efficacy of these preparations when counselling patients regarding contraceptive method selection.

Oral contraceptives do not protect against sexually transmitted diseases (STDs) including HIV/AIDS. For protection against STDs, it is advisable to use latex condoms in combination with oral contraceptives.

Adverse Reactions: An increased risk of the following serious adverse reactions has been associated with the use of oral contraceptives: thrombophlebitis; pulmonary embolism; mesenteric thrombosis; neuro-ocular lesions, e.g., retinal thrombosis; myocardial infarction; cerebral thrombosis; cerebral hemorrhage; hypertension; benign hepatic tumors; gallbladder disease.

The following adverse reactions also have been reported in patients receiving oral contraceptives: Nausea and vomiting, usually the most common adverse reactions, occur in approximately 10% or less of patients during the first cycle. Other reactions, as a general rule, are seen less frequently or only occasionally.

Other Adverse Reactions: gastrointestinal symptoms (such as abdominal cramps and bloating); breakthrough bleeding; spotting; change in menstrual flow; dysmenorrhea; amenorrhea during and after treatment; infertility after discontinuance of treatment; edema; chloasma or melasma which may persist; breast changes: tenderness, enlargement, and secretion; change in weight (increase or decrease); endocervical hyperplasias; possible diminution in lactation when given immediately post-partum; cholestatic jaundice; migraine; increase in size of uterine leiomyomata; rash (allergic); mental depression; reduced tolerance to carbohydrates; vaginal candidiasis; premenstrual-like syndrome; intolerance to contact lenses; change in corneal curvature (steepening); cataracts; optic neuritis; retinal thrombosis; changes in libido; chorea; changes in appetite; cystitis-like syndrome; rhinitis; headache; nervousness; dizziness; hirsutism; loss of scalp hair; erythema multiforme; erythema nodosum; hemorrhagic eruption; vaginitis; porphyria; impaired renal function; Raynaud’s phenomenon; auditory disturbances; hemolytic uremic syndrome; pancreatitis; arterial thromboembolism.

Symptoms And Treatment Of Overdose: Symptoms and Treatment: Numerous cases of the ingestion by children of estrogen-progestogen combinations have been reported. Although mild nausea may occur, there appears to be no other reaction. Treatment should be limited to a laxative such as citrate of magnesia with the aim of removing unabsorbed material as rapidly as possible.

Dosage And Administration: Information for the Patient on How to Take the Birth Control Pill:

1. Read these directions:

before you start taking your pills, and

any time you are not sure what to do.

2. Look at your pill pack to see if it has 21 or 28 pills:

21-Pill Pack: 21 active pills (with hormones) taken daily for 3 weeks, and then take no pills for 1 week or

28-Pill Pack: 21 active pills (with hormones) taken daily for 3 weeks, and then 7 “reminder” pills (no hormones) taken daily for 1 week.

Also check the pill pack for instructions on (1) where to start and (2) directions to take pills (see package insert for illustrations).

3. It is recommended that you use a second method of birth control (e.g., latex condoms and spermicidal foam or gel) for the first 7 days of the first cycle of pill use. This will provide a back-up in case pills are forgotten while you are getting used to taking them.

4. When receiving any medical treatment, be sure to tell your doctor that you are using birth control pills.

5. Many women have spotting or light bleeding or may feel sick to their stomach during the first 3 months on the pill. If you do feel sick, do not stop taking the pill. The problem will usually go away. If it does not go away, check with your doctor or clinic.

6. Missing pills also can cause some spotting or light bleeding, even if you make up the missed pills. You also could feel a little sick to your stomach on the days you take 2 pills to make up for missed pills.

7. If you miss pills at any time, you could get pregnant. The greatest risks for pregnancy are:

when you start a pack late, or

when you miss pills at the beginning or at the very end of the pack.

8. Always be sure you have ready:

another kind of birth control (such as latex condoms and spermicidal foam or gel) to use as a backup in case you miss pills, and

an extra, full pack of pills.

9. If you experience vomiting or diarrhea, or if you take certain medicines, such as antibiotics, your pills may not work as well. Use a backup method, such as latex condoms and spermicidal foam or gel, until you can check with your doctor or clinic.

10. If you forget more than 1 pill 2 months in a row, talk to your doctor or clinic about how to make pill-taking easier or about using another method of birth control.

11. If your questions are not answered here, call your doctor or clinic.

When to start the first pack of pills: Be sure to read these instructions:

before you start taking your pills, and

any time you are not sure what to do.

Decide with your doctor or clinic what is the best day for you to start taking your first pack of pills. Your pills may be either a 21-day or a 28-day type.

A. 21-Day Combination: With this type of birth control pill, you are on pills for 21 days and off pills for 7 days. You must not be off the pills for more than 7 days in a row.

1. The first day of your menstrual period (bleeding) is Day 1 of your cycle. Your doctor may advise you to start taking the pills on Day 1, on Day 5, or on the first Sunday after your period begins. If your period starts on Sunday, start that same day.

2. Take 1 pill at approximately the same time every day for 21 days; then take no pills for 7 days. Start a new pack on the 8th day. You will probably have a period during the 7 days off the pill. (This bleeding may be lighter and shorter than your usual period.)

B. 28-Day Combination: With this type of birth control pill, you take 21 pills which contain hormones and 7 pills which contain no hormones.

1. The first day of your menstrual period (bleeding) is Day 1 of your cycle. Your doctor may advise you to start taking the pills on Day 1, on Day 5, or on the first Sunday after your period begins. If your period starts on Sunday, start that same day.

2. Take 1 pill at approximately the same time every day for 28 days. Begin a new pack the next day, not missing any days on the pills. Your period should occur during the last 7 days of using that pill pack.

What to do during the month:

1. Take a pill at approximately the same time every day until the pack is empty.

Try to associate taking your pill with some regular activity like eating a meal or going to bed.

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

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

2. When you finish a pack:

21 pills: Wait 7 days to start the next pack. You will have your period during that week.

28 pills: Start the next pack on the next day. Take 1 pill every day. Do not wait any days between packs.

What to do if you miss pills: Table I outlines the actions you should take if you miss 1 or more of your birth control pills. Match the number of pills missed with the appropriate starting time for your type of pill pack.

Norinyl 1/50 What To Do If You Miss Pills

Sunday Start Miss 1 pill Take it as soon as you remember, and take the next pill at the usual time. This means that you might take 2 pills in one day. Miss 2 pills in a row First 2 Weeks: 1. Take 2 pills the day you remember and 2 pills the next day. 2. Then take 1 pill a day until you finish the pack. 3. Use a backup method of birth control if you have sex in the 7 days after you miss the pills. Third Week: 1. Keep taking 1 pill a day until Sunday. 2. On Sunday, safely discard the rest of the pack and start a new pack that day. 3. Use a back-up method of birth control if you have sex in the 7 days after you miss the pills. 4. You may not have a period this month. If you miss 2 periods in a row, call your doctor or clinic. Miss 3 pills or more pills in a row Anytime in the Cycle: 1. Keep taking 1 pill a day until Sunday. 2. On Sunday, safely discard the rest of the pack and start a new pack that day. 3. Use a back-up method of birth control if you have sex in the 7 days after you miss the pills. 4. You may not have a period this month. If you miss 2 periods in a row, call your doctor or clinic.

Other Than Sunday Start Miss 1 pill Take it as soon as you remember, and take the next pill at the usual time. This means that you might take 2 pills in one day. Miss 2 pills in a row First 2 Weeks: 1. Take 2 pills the day you remember and 2 pills the next day. 2. Then take 1 pill a day until you finish the pack. 3. Use a backup method of birth control if you have sex in the 7 days after you miss the pills. Third Week: 1. Safely dispose of the rest of the pill pack and start a new pack that same day. 2. Use a back-up method of birth control if you have sex in the 7 days after you miss the pills. 3. You may not have a period this month. If you miss 2 periods in a row, call your doctor or clinic. Miss 3 or more pills in a row Anytime in the Cycle: 1. Safely dispose of the rest of the pill pack and start a new pack that same day. 2. Use a back-up method of birth control if you have sex in the 7 days after you miss the pills. 3. You may not have a period this month. If you miss 2 periods in a row, call your doctor or clinic.

Note: 28-Day Pack: If you forget any of the 7 orange “reminder” pills (without hormones) in Week 4, just safely dispose of the pills you missed. Then keep taking 1 pill each day until the pack is empty. You do not need to use a backup method.

Always be sure you have on hand:

a backup method of birth control (such as latex condoms and spermicidal foam or gel) in case you miss pills, and

an extra, full pack of pills.

If you forget more than 1 pill 2 months in a row, talk to your doctor or clinic about ways to make pill-taking easier or about using another method of birth control.

Dosage And Administration: A. 21-Day Pack: With this type of birth control pill, the patient is 21 days on pills with 7 days off pills. The patient must not be off the pills for more than 7 days in a row.

1. The first day of the patient’s menstrual period (bleeding) is day 1 of a cycle. The doctor may advise the patient to start taking the pills on Day 1, on Day 5, or on the first Sunday after a period begins. If a period starts on Sunday, the patient starts that same day.

2. The pack must be labelled correctly before starting. The pack is pre-printed with a Sunday starting day. If the patient is starting on a day other than a Sunday, she should use the Flexi-start sticker labels provided. The patient peels off the label with the chosen starting day and applies it over the pre-printed days on top of the card.

3. The patient takes 1 pill at approximately the same time every day for 21 days; then she takes no pills for 7 days. She starts a new pack on the 8th day. She will probably have a period during the 7 days off the pill. (This bleeding may be lighter and shorter than a usual period.)

B. 28-Day Pack: With this type of birth control pill, the patient takes 21 pills which contain hormones and 7 pills which contain no hormones.

1. The first day of the patient’s menstrual period (bleeding) is day 1 of a cycle. The doctor may advise the patient to start taking the pills on Day 1, on Day 5, or on the first Sunday after a period begins. If a period starts on Sunday, the patient starts that same day.

2. The pack must be labelled correctly before starting. The pack is pre-printed with a Sunday starting day. If the patient is starting on a day other than a Sunday, she should use the Flexi-start sticker labels provided. The patient peels off the label with the chosen starting day and applies it over the pre-printed days on top of the card.

3. The patient takes 1 pill at approximately the same time every day for 28 days. She begins a new pack the next day, not missing any days on the pills. The patient’s period should occur during the last 7 days of using that pill pack.

What to do during the month:

1. The patient takes a pill at approximately the same time every day until the pack is empty.

The patient should try to associate taking the pill with some regular activity like eating a meal or going to bed.

The patient must not skip pills even if she has bleeding between monthly periods or feels sick to her stomach (nausea).

The patient must not skip pills even if she does not have sex very often.

2. When a pack is finished:

21 Pills: The patient must wait 7 days to start the next pack. A period will begin during that week.

28 Pills: The patient starts the next pack on the next day. She takes 1 pill every day. She does not wait any days between packs.

Availability And Storage: Norinyl 1/50 (21’s): Each white circular tablet, impressed “SEARLE” on one side and “1” on one other, contains: norethindrone 1 mg and mestranol 0.05 mg. Nonmedicinal ingredients: Active tablets: cornstarch, lactose hydrous, magnesium stearate and polyvidone. Tartrazine-free. Dispensers of 21 tablets.

Norinyl 1/50 (28’s): Each dispenser contains the same tablets as Norinyl 1/50 (21) plus 7 plain orange-colored tablets, impressed “SEARLE” on one side and P on the other, containing inert ingredients. Nonmedicinal ingredients: placebo tablets: FD&C Yellow No. 6 Lake, lactose, lactose monohydrate, magnesium stearate and microcrystalline cellulose. Tartrazine-free. Dispensers of 28 tablets.

NORINYL┬« 1/50 Searle Norethindrone – Mestranol Oral Contraceptive

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