Ortho-Novum (Norethindrone / Mestranol)

ORTHO-NOVUM® 1/50

Janssen-Ortho

Norethindrone – Mestranol

Oral Contraceptive

Action And Clinical Pharmacology: Acts through the mechanism of gonadotropin suppression primarily at the pituitary-ovarian axis with secondary pelvic involvement.

Conception Control: The contraceptive efficacy is attributed to suppression of ovulation with a possible contribution from alterations in cervical mucus and in the endometrium.

Amenorrhea: Where normal cycling does not occur, as in amenorrhea, the temporary cyclic administration of Ortho-Novum 1/50 Tablets, which tends to promote shedding of the endometrium during the therapeutic regimen, may result in rhythmic menstruation without exogenous hormonal support when product administration is discontinued.

Dysfunctional Uterine Bleeding: Dysfunctional uterine bleeding in the absence of disease or pathology is generally attributed to endocrine abnormality. Most frequently a disorder or imbalance of the pituitary-ovarian axis is responsible. Again, the temporary cyclic administration of Ortho-Novum 1/50 Tablets may result in rhythmic menstruation without exogenous hormonal support when product administration is discontinued.

Dysmenorrhea: Clinical experience has demonstrated a frequent association between anovulatory cycles and menstruation unaccompanied by dysmenorrhea.

Endometriosis: Signs and symptoms of endometriosis generally regress during administration of the tablets due in part to anovulation brought about by suppression of gonadotropic activity and in part to the transformation of functioning endometrium into decidua-like tissue by increasing levels of estrogen and progestogen.

Indications And Clinical Uses: For conception control in circumstances where lower dosage estrogen formulations prove to be unacceptable. Ortho-Novum 1/50 Tablets are also indicated for hormonal therapy, i.e., amenorrhea, dysmenorrhea, endometriosis and dysfunctional uterine bleeding.

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; known or suspected carcinoma of the breast; 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 by 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, non-smoking 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:

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

B. Conditions which predispose to venous stasis and to vascular thrombosis (e.g., immobilization after accidents or confinement to bed during long-term illness). Other non-hormonal 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 Follow-up: 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. A Papanicolaou smear should be taken if the patient has been sexually active.

The first follow-up 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: Oral contraceptives should not be taken by pregnant women. However, if conception accidentally occurs while taking the pill, there is no conclusive evidence that the estrogen and progestin contained in the oral contraceptive will damage the developing child.

Lactation: In breastfeeding women, the use of oral contraceptives results in the hormonal components being excreted in breast milk and may reduce its quantity and quality. If the use of oral contraceptives is initiated after the establishment of lactation, there does not appear to be any effect on the quantity and quality of the milk. There is no evidence that low-dose oral contraceptives are harmful to the nursing infant.

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 the jaundice should prove 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 (adenoma and focal nodular hyperplasia) have been reported, particularly in long-term users of oral contraceptives. Although these lesions are extremely rare, they have caused fatal intra-abdominal hemorrhage and should be considered in women 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 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 Disease: 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 for 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 an 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, estrogen-containing drugs 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 discontinuation 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.

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

Liver Function Tests: Bromsulphthalein Retention Test (BSP), moderate increase; AST and GGT, minor increase; alkaline phosphatase, variable increase; serum bilirubin, increased, particularly in conditions predisposing to or associated with hyperbilirubinemia.

Coagulation Tests: Factors II, VII, IX, X, XII and XIII, increased; Factor VIII, mild increase; platelet aggregation and adhesiveness, mild increase in response to common aggregating agents; fibrinogen, increased; plasminogen, mild increase; antithrombin III, mild decrease; prothrombin time, increased.

Thyroid Function Tests: Protein-bound Iodine (PBI), increased; Total Serum Thyroxine (T4), increased; Thyroid Stimulating Hormone (TSH), unchanged.

Adrenocortical Function Tests: plasma cortisol, increased.

Miscellaneous Tests: serum folate, occasionally decreased; glucose tolerance test, variable increase with return to normal after 6 to 12 months; insulin response, mild to moderate increase; c-peptide response, mild to moderate increase.

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 menstrual 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 – Post-surgery: There is an increased risk of 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 (see Tables I and II). 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.

Non-contraceptive Benefits of Oral Contraceptives: Several health advantages other than contraception have been reported.

1. Combination oral contraceptives reduce the incidence of cancer of the endometrium and ovaries.

2. Oral contraceptives reduce the likelihood of developing benign breast disease and, as a result, decrease the incidence of breast biopsies.

3. Oral contraceptives reduce the likelihood of development of functional ovarian cysts.

4. Pill users have less menstrual blood loss and have more regular cycles, thereby reducing the chance of developing iron-deficiency anemia.

5. The use of oral contraceptives may decrease the severity of dysmenorrhea and premenstrual syndrome, and may improve acne vulgaris, hirsutism, and other androgen-mediated disorders.

6. Oral contraceptives decrease the incidence of acute pelvic inflammatory disease and, thereby, reduce as well the incidence of ectopic pregnancy.

7. Oral contraceptives have potential beneficial effects on endometriosis.

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 reaction, occurs in approximately 10% or less of patients during the first cycle. Other reactions, as a general rule, are seen less frequently or only occasionally, as follows: gastrointestinal symptoms (such as abdominal cramps and bloating); breakthrough bleeding; spotting; change in menstrual flow; dysmenorrhea; amenorrhea during and after treatment; temporary 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 postpartum; cholestatic jaundice; migraine; increase in size of uterine leiomyomata; rash (allergic); 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.

Symptoms And Treatment Of Overdose: Symptoms and Treatment: In case of overdosage or accidental ingestion by children, the physician should observe the patient closely although generally no treatment is required. Gastric lavage may be utilized if considered necessary.

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 taken 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. You may wish to 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 back-up 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 back-up 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 21 days on the pill with 7 days off the pill. 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. The pills may be started up to Day 6 of your cycle. Your starting day will be chosen in discussion with your doctor. You will always begin taking your pill on this day of the week. 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.)

Directions: 21-Day Regimen: Follow these instructions carefully (see package insert for illustrations): Your starting day will be chosen in discussion with your doctor. You should always begin taking your tablets on this day of the week. To set the package to the day you and your doctor selected, insert a coin into the middle slot and turn the inner wheel counterclockwise until that day appears in the window. The example shown is for a Sunday start. Your first yellow tablet is below the “V” notch as shown. Ensure that the tab marked “Lift Out” is set over this tablet. Break off the tab and begin tablet taking. To take your second and all subsequent tablets, turn the clear outer cover clockwise to the next available tablet. Take a tablet a day, for 21 days, completing all yellow tablets. After you have taken all of your tablets wait seven days and begin your next package on your chosen starting day whether you have finished menstruating or not. Always remember to set the starting day of each new package to the day chosen by you and your doctor.

Your first pill of each package is always under the “V” notch.

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. The pills may be started up to Day 6 of your cycle. Your starting day will be chosen in discussion with your doctor. You will always begin taking your pill on this day of the week. 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.

Directions: 28-Day Regimen: Follow these directions carefully (see package insert for illustrations): Always complete the yellow tablets before taking the green tablets.

Your starting day will be chosen in discussion with your doctor. You should always begin taking your tablets on this day of the week. To set the package to the day you and your doctor selected, insert a coin into the middle slot and turn the inner wheel counterclockwise until that day appears in the window. The example shown is for a Sunday start. Your first yellow tablet is immediately to the right of the green tablets and below the “V” notch as shown. Ensure that the tab marked “Lift Out” is set over this tablet. Break off the tab and begin tablet taking. To take your second and all subsequent tablets, turn the clear outer cover clockwise to the next available tablet. Take a tablet a day, every day, first completing all 21 yellow tablets, and finally the 7 green tablets. After you have taken all of your tablets, begin your next package the very next day on your chosen starting day, whether you have finished menstruating or not. Always remember to set the starting day of each new package to the day chosen by you and your doctor.

Your first pill of each package is always under the “V” notch.

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 such as 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 III 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.

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 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 back-up 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 “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 back-up method.

Always be sure you have on hand:

a back-up 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. Talk about ways to make pill-taking easier or about using another method of birth control.

Hormonal Therapy: The requirement for continued therapy should be assessed periodically

Availability And Storage: 21-day Regimen: Each yellow, unscored tablet, engraved on each side with “ORTHO 150”, contains: norethindrone 1 mg and mestranol 50 g. Nonmedicinal ingredients: D&C Yellow No. 10 Lake, lactose, magnesium stearate, polyvinylpyrrolidone and starch. Tartrazine-free. Packaged in green VARIDATE DIALPAK Tablet Dispenser Units.

28-day Regimen: Each yellow tablet, engraved on both sides with “ORTHO 150”, contains: norethindrone 1 mg and mestranol 50 g. Nonmedicinal ingredients: D&C Yellow No. 10 Lake, lactose, magnesium stearate, polyvinylpyrrolidone and starch. Each green tablet, embossed on each side with word “ORTHO”, contains inert ingredients. Nonmedicinal ingredients: D&C Yellow No. 10 Lake, FD&C Blue No. 2 Lake, lactose, magnesium stearate, microcrystalline cellulose and starch. Tartrazine-free. Packaged in white VARIDATE DIALPAK Tablet Dispenser Units.

Store between 15 and 30°C. Leave contents in protective packaging until time of use. (Shown in Product Recognition Section)

ORTHO-NOVUM® 1/50 Janssen-Ortho Norethindrone – Mestranol Oral Contraceptive

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