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Demulen® 1/35-21
Demulen® 1/35-28

Demulen® 1/50-21
Demulen® 1/50-28

(ethynodiol diacetate with ethinyl estradiol)


DESCRIPTIONCLINICAL PHARMACOLOGYINDICATIONS AND USAGECONTRAINDICATIONSWARNINGSPRECAUTIONSINFORMATION FOR THE PATIENTADVERSE REACTIONSOVERDOSAGENON-CONTRACEPTIVE HEALTH BENEFITSDOSAGE AND ADMINISTRATIONHOW SUPPLIEDREFERENCES

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Patients should be counseled that this product does not protect against HIV infection (AIDS) and other sexually transmitted diseases.

ORAL CONTRACEPTIVE AGENTS


DESCRIPTION

Demulen 1/35-21 and Demulen 1/35-28. Each white tablet contains 1 mg of ethynodiol diacetate and 35 mcg of ethinyl estradiol, and the inactive ingredients include calcium acetate, calcium phosphate, corn starch, hydrogenated castor oil, and povidone. Each blue tablet in the Demulen 1/35-28 package is a placebo containing no active ingredients, and the inactive ingredients include lactose monohydrate, microcrystalline cellulose, anhydrous lactose, FD&C Blue No. 1 Lake, and magnesium stearate.

Demulen 1/50-21 and Demulen 1/50-28. Each white tablet contains 1 mg of ethynodiol diacetate and 50 mcg of ethinyl estradiol, and the inactive ingredients include calcium acetate, calcium phosphate, corn starch, hydrogenated castor oil, and povidone. Each pink tablet in the Demulen 1/50-28 package is a placebo containing no active ingredients, and the inactive ingredients include lactose monohydrate, microcrystalline cellulose, anhydrous lactose, FD&C Yellow No. 6 Lake, and magnesium stearate.

The chemical name for ethynodiol diacetate is 19-nor-17alpha-pregn-4-en-20-yne-3beta,17-diol diacetate, and for ethinyl estradiol it is 19-nor-17alpha-pregna-1,3,5(10)-trien-20-yne-3,17-diol. The structural formulas are as follows:

Therapeutic class: Oral contraceptive.


CLINICAL PHARMACOLOGY

Combination oral contraceptives act primarily by suppression of gonadotropins. Although the primary mechanism of this action is inhibition of ovulation, other alterations in the genital tract, including 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) may also contribute to contraceptive effectiveness.


INDICATIONS AND USAGE

Demulen 1/35 and Demulen 1/50 are indicated for the prevention of pregnancy in women who elect to use oral contraceptives as a method of contraception.

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

Table 1. Lowest expected and typical failure rates during the first year of continuous use of a method. Percent of women experiencing an accidental pregnancy in the first year of continuous use.1,1a
Method Lowest Expected* Typical**
No contraception 85 85
Oral contraceptives
Combined 0.1 N/A***
Progestogen only 0.5 N/A***
Diaphragm with spermicidal cream or jelly 6 18
Spermicides alone (foam, creams, jellies and vaginal suppositories) 3 21
Vaginal sponge
Nulliparous 6 18
Parous 9 28
IUD (medicated)
Progesterone 2 N/A***
Copper T 380A 0.8 N/A***
Condom without spermicides 2 12
Periodic abstinence (all methods) 1-9 20
Progestogen injections 0.3 0.3
Progestogen implants 0.2 0.2
Female sterilization 0.2 0.4
Male sterilization 0.1 0.15
Adapted from Trussell et al.1
*The authors' best guess of the percentage of women expected to experience an accidental pregnancy among couples who initiate a method (not necessarily for the first time) and who use it consistently and correctly during the first year if they do not stop for any other reason.

**This term represents "typical" couples who initiate use of a method (not necessarily for the first time), who experience an accidental pregnancy during the first year if they do not stop for any other reason.

***N/A — Data not available.


CONTRAINDICATIONS

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


WARNINGS

Cigarette smoking increases the risk of serious cardiovascular side effects from oral contraceptive use. This risk increases with age and with heavy smoking (15 or more cigarettes per day) and is quite marked in women over 35 years of age. Women who use oral contraceptives should be strongly advised not to smoke.

The use of oral contraceptives is associated with increased risk of several serious conditions including venous and arterial thromboembolism, thrombotic and hemorrhagic stroke, myocardial infarction, liver tumors or other liver lesions, and gallbladder disease. The risk of morbidity and mortality increases significantly in the presence of other risk factors such as hypertension, hyperlipidemia, obesity, and diabetes mellitus.

Practitioners prescribing oral contraceptives should be familiar with the following information relating to these and other risks.

The information contained herein is principally based on studies carried out in patients who used oral contraceptives with formulations containing higher amounts of estrogens and progestogens than those in common use today. The effect of long-term use of the oral contraceptives with lesser amounts of both estrogens and progestogens remains to be determined.

Throughout this labeling, epidemiological studies reported are of two types: retrospective case-control studies and prospective cohort studies. Case-control studies provide an estimate of the relative risk of a disease, which is defined as the ratio of the incidence of a disease among oral contraceptive users to that among nonusers. The relative risk (or odds ratio) does not provide information about the actual clinical occurrence of a disease. Cohort studies provide a measure of both the relative risk and the attributable risk. The latter is the difference in the incidence of disease between oral contraceptive users and nonusers. The attributable risk does provide information about the actual occurrence or incidence of a disease in the subject population. For further information, the reader is referred to a text on epidemiological methods.

1. Thromboembolic disorders and other vascular problems.

a. Myocardial infarction. An increased risk of myocardial infarction has been associated with oral contraceptive use.2-21 This increased risk is primarily in smokers or in women with other underlying risk factors for coronary artery disease such as hypertension, obesity, diabetes, and hypercholesterolemia. The relative risk for myocardial infarction in current oral contraceptive users has been estimated to be 2 to 6. The risk is very low under the age of 30. However, there is the possibility of a risk of cardiovascular disease even in very young women who take oral contraceptives.

Smoking in combination with oral contraceptive use has been reported to contribute substantially to the risk of myocardial infarction in women in their mid-thirties or older, with smoking accounting for the majority of excess cases.22 Mortality rates associated with circulatory disease have been shown to increase substantially in smokers, especially in those 35 years of age and older among women who use oral contraceptives (see Figure 1, Table 2).

Figure 1. Circulatory disease mortality rates per 100,000 woman-years
by age, smoking status, and oral contraceptive use.14
Adapted from Layde and Beral.14

Oral contraceptives may compound the effects of well-known cardiovascular risk factors such as hypertension, diabetes, hyperlipidemias, hypercholesterolemia, age, cigarette smoking, and obesity. In particular, some progestogens decrease HDL cholesterol23-31 and cause glucose intolerance, while estrogens may create a state of hyperinsulinism.32 Oral contraceptives have been shown to increase blood pressure among some users (see Warning No. 9). Similar effects on risk factors have been associated with an increased risk of heart disease.

b. Thromboembolism. An increased risk of thromboembolic and thrombotic disease associated with the use of oral contraceptives is well established.17,33-51 Case-control studies have estimated the relative risk to be 3 for the first episode of superficial venous thrombosis, 4 to 11 for deep vein thrombosis or pulmonary embolism, and 1.5 to 6 for women with predisposing conditions for venous thromboembolic disease.34-37,45,46 Cohort studies have shown the relative risk to be somewhat lower, about 3 for new cases (subjects with no past history of venous thrombosis or varicose veins) and about 4.5 for new cases requiring hospitalization.42,47,48 The risk of venous thromboembolic disease associated with oral contraceptives is not related to duration of use.

A two- to seven-fold increase in relative risk of postoperative thromboembolic complications has been reported with the use of oral contraceptives.38,39 The relative risk of venous thrombosis in women who have predisposing conditions is about twice that of women without such medical conditions.43 If feasible, oral contraceptives should be discontinued at least 4 weeks prior to and for 2 weeks after elective surgery of a type associated with an increased risk of thromboembolism, and also during and following prolonged immobilization. Since the immediate postpartum period is also associated with an increased risk of thromboembolism, oral contraceptives should be started no earlier than 4 to 6 weeks after delivery in women who elect not to breast feed.

c. Cerebrovascular diseases. Both the relative and attributable risks of cerebrovascular events (thrombotic and hemorrhagic strokes) have been reported to be increased with oral contraceptive use,14,17,18,34,42,46,52-59 although, in general, the risk was greatest among older (over 35 years), hypertensive women who also smoked. Hypertension was reported to be a risk factor for both users and nonusers, for both types of strokes, while smoking increased the risk for hemorrhagic strokes.

In one large study,52 the relative risk for thrombotic stroke was reported as 9.5 times greater in users than in nonusers. It ranged from 3 for normotensive users to 14 for users with severe hypertension.54 The relative risk for hemorrhagic stroke was reported to be 1.2 for nonsmokers who used oral contraceptives, 1.9 to 2.6 for smokers who did not use oral contraceptives, 6.1 to 7.6 for smokers who used oral contraceptives, 1.8 for normotensive users, and 25.7 for users with severe hypertension. The risk is also greater in older women and among smokers.

d. Dose-related risk of vascular disease with oral contraceptives. A positive association has been reported between the amount of estrogen and progestogen in oral contraceptives and the risk of vascular disease.41,43,53,59-64 A decline in serum high density lipoproteins (HDL) has been reported with many progestogens.23-31 A decline in serum high density lipoproteins has been associated with an increased incidence of ischemic heart disease.65 Because estrogens increase HDL-cholesterol, the net effect of an oral contraceptive depends on the balance achieved between doses of estrogen and progestogen and the nature and absolute amount of progestogens used in the contraceptives. The amount of both steroids should be considered in the choice of an oral contraceptive.

Minimizing exposure to estrogen and progestogen is in keeping with good principles of therapeutics. For any particular estrogen-progestogen combination, the dosage regimen prescribed should be one that contains the least amount of estrogen and progestogen that is compatible with a low failure rate and the needs of the individual patient. New acceptors of oral contraceptives should be started on preparations containing the lowest estrogen content that produces satisfactory results in the individual.

e. Persistence of risk of vascular disease. There are three studies that have shown persistence of risk of vascular disease for users of oral contraceptives. In a study in the United States, the risk of developing myocardial infarction after discontinuing oral contraceptives persisted for at least 9 years for women 40-49 years old who had used oral contraceptives for 5 or more years, but this increased risk was not demonstrated in other age groups.16 Another American study reported former use of oral contraceptives was significantly associated with increased risk of subarachnoid hemorrhage.57 In another study, in Great Britain, the risk of developing nonrheumatic heart disease plus hypertension, subarachnoid hemorrhage, cerebral thrombosis, and transient ischemic attacks persisted for at least 6 years after discontinuation of oral contraceptives, although the excess risk was small.14,18,66 It should be noted that these studies were performed with oral contraceptive formulations containing 50 mcg or more of estrogens.

2. Estimates of mortality from contraceptive use. One study67 gathered data from a variety of sources that have estimated the mortality rates associated with different methods of contraception at different ages (Table 2). These estimates include the combined risk of death associated with contraceptive methods plus the risk attributable to pregnancy in the event of method failure. Each method of contraception has its specific benefits and risks. The study concluded that, with the exception of oral contraceptive users 35 and older who smoke and 40 or older who do not smoke, mortality associated with all methods of birth control is low and below that associated with childbirth. The observation of a possible increase in risk of mortality with age for oral contraceptive users is based on data gathered in the 1970's, but not reported until 1983.67 However, current clinical practice involves the use of lower estrogen dose formulations combined with careful restriction of oral contraceptive use to women who do not have the various risk factors listed in this labeling.

Because of these changes in practice and, also, because of some limited new data that suggest that the risk of cardiovascular disease with the use of oral contraceptives may now be less than previously observed,48,152 the Fertility and Maternal Health Drugs Advisory Committee was asked to review the topic in 1989. The Committee concluded that, although cardiovascular disease risks may be increased with oral contraceptive use after age 40 in healthy nonsmoking women (even with the newer low-dose formulations), there are greater potential health risks associated with pregnancy in older women and with the alternative surgical and medical procedures that may be necessary if such women do not have access to effective and acceptable means of contraception.

Therefore, the Committee recommended that the benefits of oral contraceptive use by healthy nonsmoking women over 40 may outweigh the possible risks. Of course, older women, as all women who take oral contraceptives, should take the lowest possible dose formulation that is effective.

Table 2. Annual number of birth-related or method-related deaths associated with control of fertility per 100,000 nonsterile women, by fertility control method according to age.67
Age
Method of control 15-19 20-24 25-29 30-34 35-39 40-44
No fertility control methods* 7.0 7.4 9.1 14.8 25.7 28.2
Oral contraceptives
nonsmoker** 0.3 0.5 0.9 1.9 13.8 31.6
smoker** 2.2 3.4 6.6 13.5 51.1 117.2
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
Adapted from Ory.67

3. Carcinoma of the breast and reproductive organs. Numerous epidemiological studies have been performed on the incidence of breast, endometrial, ovarian, and cervical cancer in women using oral contraceptives. While there are conflicting reports, most studies suggest that the use of oral contraceptives is not associated with an overall increase in the risk of developing breast cancer.17,40,68-78 Some studies have reported an increased relative risk of developing breast cancer, particularly at a young age.79-102,151 This increased relative risk appears to be related to duration of use.

Some studies suggested that oral contraceptive use was associated with an increase in the risk of cervical intraepithelial neoplasia, dysplasia, erosion, carcinoma, or microglandular dysplasia in some populations of women.17,50,103-115 However, there continues to be controversy about the extent to which such findings may be due to differences in sexual behavior and other factors.

In spite of many studies of the relationship between oral contraceptive use and breast and cervical cancers, a cause and effect relationship has not been established.

4. Hepatic neoplasia. Benign hepatic adenomas and other hepatic lesions have been associated with oral contraceptive use,116-121 although the incidence of such benign tumors is rare in the United States. Indirect calculations have estimated the attributable risk to be in the range of 3.3 cases per 100,000 for users, a risk that increases after 4 or more years of use.120 Rupture of benign, hepatic adenomas or other lesions may cause death through intra-abdominal hemorrhage. Therefore, such lesions should be considered in women presenting with abdominal pain and tenderness, abdominal mass, or shock. About one quarter of the cases presented because of abdominal masses; up to one half had signs and symptoms of acute intraperitoneal hemorrhage.121 Diagnosis may prove difficult.

Studies from the U.S.,122,150 Great Britain,123,124 and Italy125 have shown an increased risk of hepatocellular carcinoma in long-term (>8 years; relative risk of 7-20) oral contraceptive users. However, these cancers are rare in the United States, and the attributable risk (the excess incidence) of liver cancers in oral contraceptive users approaches less than 1 per 1,000,000 users.

5. Ocular lesions. There have been reports of retinal thrombosis and other ocular lesions associated with the use of oral contraceptives. Oral contraceptives should be discontinued if there is unexplained, gradual or sudden, partial or complete loss of vision; onset of proptosis or diplopia; papilledema; or any evidence of retinal vascular lesions. Appropriate diagnostic and therapeutic measures should be undertaken immediately.

6. Oral contraceptive use before or during pregnancy. Extensive epidemiological studies have revealed no increased risk of birth defects in women who have used oral contraceptives prior to pregnancy.126, 129 The majority of recent studies also do not suggest a teratogenic effect, particularly insofar as cardiac anomalies and limb reduction defects are concerned,126-129 when the pill is taken inadvertently during early pregnancy.

The administration of oral contraceptives to induce withdrawal bleeding should not be used as a test for pregnancy. Oral contraceptives should not be used during pregnancy to treat threatened or habitual abortion. It is recommended that for any patient who has missed two consecutive periods, pregnancy should be ruled out before continuing oral contraceptive use. If the patient has not adhered to the prescribed schedule, the possibility of pregnancy should be considered at the time of the first missed period and further use of oral contraceptives should be withheld until pregnancy has been ruled out. Oral contraceptive use should be discontinued if pregnancy is confirmed.

7. Gallbladder disease. Earlier studies reported an increased lifetime relative risk of gallbladder surgery in users of oral contraceptives and estrogens.40,42,53,70 More recent studies, however, have shown that the relative risk of developing gallbladder disease among oral contraceptive users may be minimal.130-132 The recent findings of minimal risk may be related to the use of oral contraceptive formulations containing lower doses of estrogens and progestogens.

8. Carbohydrate and lipid metabolic effects. Oral contraceptives have been shown to cause a decrease in glucose tolerance in a significant percentage of users.32 This effect has been shown to be directly related to estrogen dose.133 Progestogens increase insulin secretion and create insulin resistance, the effect varying with different progestational agents.32,134 However, in the nondiabetic woman, oral contraceptives appear to have no effect on fasting blood glucose. Because of these demonstrated effects, prediabetic and diabetic women should be carefully observed while taking oral contraceptives.

Some women may have persistent hypertriglyceridemia while on the pill. As discussed earlier (see Warnings 1a and 1d), changes in serum triglycerides and lipoprotein levels have been reported in oral contraceptive users.23-31,135,136

9. Elevated blood pressure. An increase in blood pressure has been reported in women taking oral contraceptives50,53,137-139 and this increase is more likely in older oral contraceptive users137 and with extended duration of use.53 Data from the Royal College of General Practitioners138 and subsequent randomized trials have shown that the incidence of hypertension increases with increasing concentrations of progestogens.

Women with a history of hypertension or hypertension-related diseases, or renal disease139 should be encouraged to use another method of contraception. If such women elect to use oral contraceptives, they should be monitored closely and if significant elevation of blood pressure occurs, oral contraceptives should be discontinued. For most women, elevated blood pressure will return to normal after stopping oral contraceptives,137 and there is no difference in the occurrence of hypertension among ever- and never-users.140

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

11. Bleeding irregularities. Breakthrough bleeding and spotting are sometimes encountered in patients on oral contraceptives, especially during the first three months of use. Nonhormonal causes should be considered and adequate diagnostic measures taken to rule out malignancy or pregnancy in the event of breakthrough bleeding, as in the case of any abnormal vaginal bleeding. If a pathologic basis has been excluded, time alone or a change to another formulation may solve the problem. In the event of amenorrhea, pregnancy should be ruled out.


PRECAUTIONS

1. Physical examination and follow-up. It is good medical practice for all women to have annual history and physical examinations, including women using oral contraceptives. The physical examination, however, may be deferred until after initiation of oral contraceptives if requested by the woman and judged appropriate by the clinician. The physical examination should include special reference to blood pressure, breasts, abdomen, and pelvic organs, including cervical cytology, and relevant laboratory tests. In case of undiagnosed, persistent, or recurrent abnormal vaginal bleeding, appropriate measures should be conducted to rule out malignancy. Women with a strong family history of breast cancer or who have breast nodules should be monitored with particular care.

2. Lipid disorders. Women who are being treated for hyperlipidemias should be followed closely if they elect to use oral contraceptives. Some progestogens may elevate LDL levels and may render the control of hyperlipidemias more difficult.

3. Liver function. If jaundice develops in any woman receiving oral contraceptives, they should be discontinued. Steroids may be poorly metabolized in patients with impaired liver function and should be administered with caution in such patients. Cholestatic jaundice has been reported after combined treatment with oral contraceptives and troleandomycin. Hepatotoxicity following a combination of oral contraceptives and cyclosporine has also been reported.

4. Fluid retention. Oral contraceptives may cause some degree of fluid retention. They should be prescribed with caution, and only with careful monitoring, in patients with conditions that might be aggravated by fluid retention, such as convulsive disorders, migraine syndrome, asthma, or cardiac, hepatic, or renal dysfunction.

5. Emotional disorders. Women with a history of depression should be carefully observed and the drug discontinued if depression recurs to a serious degree.

6. Contact lenses. Contact lens wearers who develop visual changes or changes in lens tolerance should be assessed by an ophthalmologist.

7. Drug interactions. Reduced efficacy and increased incidence of breakthrough bleeding and menstrual irregularities have been associated with concomitant use of rifampin. A similar association, though less marked, has been suggested for barbiturates, phenylbutazone, phenytoin sodium, and possibly with griseofulvin, ampicillin, and tetracyclines.

8. Laboratory test interactions. Certain endocrine and liver function tests and blood components may be affected by oral contraceptives:

  1. Increased prothrombin and factors VII, VIII, IX, and X; decreased antithrombin III; increased platelet aggregability.
  2. Increased thyroid binding globulin (TBG), leading to increased circulating total thyroid hormone as measured by protein-bound iodine (PBI), T4 by column or by radioimmunoassay. Free T3 resin uptake is decreased, reflecting the elevated TBG; free T4 concentration is unaltered.
  3. Other binding proteins may be elevated in the serum.
  4. Sex-steroid binding globulins are increased and result in elevated levels of total circulating sex steroids and corticoids; however, free or biologically active levels remain unchanged.
  5. Triglycerides and phospholipids may be increased.
  6. Glucose tolerance may be decreased.
  7. Serum folate levels may be depressed. This may be of clinical significance if a woman becomes pregnant shortly after discontinuing oral contraceptives.
  8. Increased sulfobromophthalein and other abnormalities in liver function tests may occur.
  9. Plasma levels of trace minerals may be altered.
  10. Response to the metyrapone test may be reduced.

9. Carcinogenesis. See Warnings.

10. Pregnancy. Pregnancy Category X. See Contraindications and Warnings.

11. Nursing mothers. Small amounts of oral contraceptive steroids have been identified in the milk of nursing mothers141-143 and a few adverse effects on the child have been reported, including jaundice and breast enlargement. In addition, oral contraceptives given in the postpartum period may interfere with lactation by decreasing the quantity and quality of breast milk. If possible, the nursing mother should be advised not to use oral contraceptives, but to use other forms of contraception until she has completely weaned her child.

12. Pediatric use. Safety and effectiveness in pediatric patients have not been established.

13. Venereal diseases. Oral contraceptives are of no value in the prevention or treatment of venereal disease. The prevalence of cervical Chlamydia trachomatis and Neisseria gonorrhoeae in oral contraceptive users is increased several-fold.144,145 It should not be assumed that oral contraceptives afford protection against pelvic inflammatory disease from chlamydia.144 Patients should be counseled that this product does not protect against HIV infection (AIDS) and other sexually transmitted diseases.

14. General.

  1. The pathologist should be advised of oral contraceptive therapy when relevant specimens are submitted.
  2. Treatment with oral contraceptives may mask the onset of the climacteric. (See Warnings regarding risks in this age group.)

INFORMATION FOR THE PATIENT

See patient labeling section.


ADVERSE REACTIONS

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

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

The following adverse reactions have been reported in patients receiving oral contraceptives and are believed to be drug-related:

The following adverse reactions or conditions have been reported in users of oral contraceptives and the association has been neither confirmed nor refuted:


OVERDOSAGE

Serious ill effects have not been reported following acute ingestion of large doses of oral contraceptives by young children.180,181 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 that largely utilized oral contraceptive formulations containing estrogen doses exceeding 35 mcg of ethinyl estradiol or 50 mcg of mestranol.148,149

Effects on menses:

Effects related to inhibition of ovulation:

Effects from long-term use:


DOSAGE AND ADMINISTRATION

To achieve maximum contraceptive effectiveness, oral contraceptives must be taken exactly as directed and at intervals of 24 hours.

IMPORTANT: If the Sunday start schedule is selected, the patient should be instructed to use an additional method of protection until after the first week of administration in the initial cycle. The possibility of ovulation and conception prior to initiation of use should be considered.


Demulen 1/35-21, Demulen 1/35-28,
Demulen 1/50-21, and Demulen 1/50-28
Dosage Schedules

The Demulen 1/35-21 and Demulen 1/50-21 Compack® tablet dispensers contain 21 tablets arranged in three numbered rows of 7 tablets each.

The Demulen 1/35-28 and Demulen 1/50-28 tablet dispensers contain 21 white active tablets arranged in three numbered rows of 7 tablets each, followed by a fourth row of 7 pink (blue for Demulen 1/35-28) placebo tablets.

Days of the week are printed above the tablets, starting with Sunday on the left.

Two dosage schedules are described, one of which may be more convenient or suitable than the other for an individual patient.

Schedule #1: Sunday start. The patient begins taking Demulen 1/35-21, Demulen 1/35-28, Demulen 1/50-21, or Demulen 1/50-28 from the first row of her package, one tablet daily, starting on the first Sunday after the onset of menstruation. If the patient's period begins on a Sunday she takes her first tablet that very same day. The 21st tablet or the 28th tablet, depending on whether the patient is taking the 21- or 28-tablet course, will then be taken on a Saturday.

Subsequent cycles:

21-tablet course — The patient begins a new 21-tablet course on the eighth day, Sunday, after taking her last tablet. All subsequent cycles will also begin on Sunday, one tablet being taken each day for 3 weeks followed by a week of no pill-taking.

28-tablet course — The patient begins a new 28-tablet course on the next day, Sunday, and all subsequent cycles will also begin on Sunday, one tablet being taken each and every day.

With a Sunday-start schedule, a woman whose period begins on the day of or 1 to 4 days before taking the first tablet should expect a diminution of flow and fewer menstrual days. The initial cycle will likely be shortened by from 1 to 5 days. Thereafter, cycles should be about 28 days in length.

Schedule #2: Day 1 start. The patient begins taking Demulen 1/35-21 or Demulen 1/50-21 from the first row of her package, one tablet daily, starting with the pill day which corresponds to day 1 of her menstrual cycle; the first day of menstruation is counted as day 1. After the last (Saturday) tablet in row #3 has been taken, if any remain in the first row, the patient completes her 21-tablet schedule starting with Sunday in row #1.

Subsequent cycles: The patient begins a new 21-tablet course on the eighth day after taking her last tablet, again starting the same day of the week on which she began her first course. All subsequent cycles will also begin on that same day, one tablet being taken each day for 3 weeks followed by a week of no pill-taking.

Special notes

Spotting, breakthrough bleeding, or nausea. If spotting (bleeding insufficient to require a pad), breakthrough bleeding (heavier bleeding similar to a menstrual flow), or nausea occurs the patient should continue taking her tablets as directed. The incidence of spotting, breakthrough bleeding, or nausea is minimal, most frequently occurring in the first cycle. Ordinarily spotting or breakthrough bleeding will stop within a week. Usually the patient will begin to cycle regularly within two or three courses of tablet-taking. In the event of spotting or breakthrough bleeding organic causes should be borne in mind. (See Warnings No. 11.)

Missed menstrual periods. Withdrawal flow will normally occur 2 or 3 days after the last active tablet is taken. Failure of withdrawal bleeding ordinarily does not mean that the patient is pregnant, providing the dosage schedule has been correctly followed. (See Warnings No. 6.)

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 two consecutive periods, pregnancy should be ruled out before continuing the contraceptive regimen.

The first intermenstrual interval after discontinuing the tablets is usually prolonged; consequently, a patient for whom a 28-day cycle is usual might not begin to menstruate for 35 days or longer. Ovulation in such prolonged cycles will occur correspondingly later in the cycle. Posttreatment cycles after the first one, however, are usually typical for the individual woman prior to taking tablets. (See Warnings No. 11.)

Missed tablets. If a woman misses taking one active tablet the missed tablet should be taken as soon as it is remembered. In addition, the next tablet should be taken at the usual time. If two consecutive active tablets are missed in week 1 or week 2 of the pack, the dosage should be doubled for the next 2 days. The regular schedule should then be resumed, but an additional method of protection must be used as a backup for the next 7 days if she has sex during that time or she may become pregnant.

If two consecutive active tablets are missed in week 3 of the pack or three consecutive active tablets are missed during any of the first 3 weeks of the pack, direct the patient to do one of the following: Day 1 Starters should discard the rest of the pack and begin a new pack that same day; Sunday Starters should continue to take 1 tablet daily until Sunday, discard the rest of the pack, and begin a new pack that same day. The patient may not have a period this month; however, if she has missed two consecutive periods, pregnancy should be ruled out. An additional method of protection must be used as a backup for the next 7 days after the tablets are missed if she has sex during that time or she may become pregnant.

While there is little likelihood of ovulation if only one active tablet is missed, the possibility of spotting or breakthrough bleeding is increased and should be expected if two or more successive active tablets are missed. However, the possibility of ovulation increases with each successive day that scheduled active tablets are missed.

If one or more placebo tablets of Demulen 1/35-28 or Demulen 1/50-28 are missed, the Demulen 1/35-28 or Demulen 1/50-28 schedule should be resumed on the following Sunday (the eighth day after the last white tablet was taken). Omission of placebo tablets in the 28-tablet courses does not increase the possibility of conception provided that this schedule is followed.


HOW SUPPLIED

Demulen 1/35:

Each white Demulen 1/35 tablet is round in shape, with a debossed SEARLE on one side and 151 and design on the other side, and contains 1 mg of ethynodiol diacetate and 35 mcg of ethinyl estradiol.

Demulen 1/35-21 is packaged in cartons of 6 and 24 Compack tablet dispensers of 21 tablets each.

Demulen 1/35-28 is packaged in cartons of 6 and 24 Compack tablet dispensers. Each Compack contains 21 white Demulen 1/35 tablets and 7 blue placebo tablets. (Placebo tablets have a debossed SEARLE on one side and a "P" on the other side.)

Demulen 1/50:

Each white Demulen 1/50 tablet is round in shape, with a debossed SEARLE on one side and 71 on the other side, and contains 1 mg of ethynodiol diacetate and 50 mcg of ethinyl estradiol.

Demulen 1/50-21 is packaged in cartons of 6 and 24 Compack tablet dispensers of 21 tablets each.

Demulen 1/50-28 is packaged in cartons of 6 and 24 Compack tablet dispensers. Each Compack contains 21 white Demulen 1/50 tablets and 7 pink placebo tablets. (Placebo tablets have a debossed SEARLE on one side and a "P" on the other side.)

Caution: Federal law prohibits dispensing without prescription.


REFERENCES

1. Trussell J, et al. Stud Fam Plann. 1987;18(Sept-Oct):237; and 1990;21(Jan-Feb):51. 1a. Physicians' Desk Reference. 47th ed. Oradell, NJ: Medical Economics Co Inc; 1993:2598-2601. 2. Mann JI, et al. Br Med J. 1975;2(May 3):241. 3. Mann JI, et al. Br Med J. 1975;3(Sept 13):631. 4. Mann JI, et al. Br Med J. 1975;2(May 3):245. 5. Mann JI, et al. Br Med J. 1976;2(Aug 21):445. 6. Arthes FG, et al. Chest. 1976;70(Nov):574. 7. Jain AK. Am J Obstet Gynecol. 1976;301(Oct 1):126; and Stud Fam Plann. 1977;8(March):50. 8. Ory HW. JAMA. 1977;237(June 13):2619. 9. Jick H, et al. JAMA. 1978;239(April 3):1403,1407. 10. Jick H, et al. JAMA. 1978;240(Dec 1):2548. 11. Shapiro S, et al. Lancet. 1979;1(April 7):743. 12. Rosenberg L, et al. Am J Epidemiol. 1980;111(Jan):59. 13. Krueger DE, et al. Am J. Epidemiol. 1980;111(June):655. 14. Layde P, et al. Lancet. 1981;1(March 7):541. 15. Adam SA, et al. Br J Obstet Gynaecol. 1981;88(Aug):838. 16. Slone D, et al. N Engl J Med. 1981;305(Aug 20):420. 17. Ramcharan S, et al. The Walnut Creek Contraceptive Drug Study. Vol 3. US Govt Ptg Off; 1981; and J Reprod Med. 1980;25(Dec):346. 18. Layde PM, et al. J R Coll Gen Pract. 1983;33(Feb):75. 19. Rosenberg L, et al. JAMA. 1985;253(May 24/31):2965. 20. Mant D, et al. J Epidemiol Community Health. 1987;41(Sept):215. 21. Croft P, et al. Br Med J. 1989;298(Jan 21):165. 22. Goldbaum GM, et al. JAMA. 1987;258(Sept 11):1339. 23. Bradley DD, et al. N Engl J Med. 1978;299(July 6):17. 24. Tikkanen MJ. J Reprod Med. 1986;31(Sept suppl):898. 25. Lipson A, et al. Contraception. 1986;34(Aug):121. 26. Burkman RT, et al. Obstet Gynecol. 1988;71(Jan):33. 27. Knopp RH. J Reprod Med. 1986;31(Sept suppl):913. 28. Krauss RM, et al. Am J Obstet Gynecol. 1983;145(Feb 15):446. 29. Wahl P, et al. N Engl J Med. 1983;308(April 14):862. 30. Wynn V, et al. Am J Obstet Gynecol. 1982;142(March 15):766. 31. LaRosa JC. J Reprod Med. 1986;31(Sept suppl):906. 32. Wynn V, et al. J Reprod Med. 1986;31(Sept suppl):892. 33. Royal College of General Practitioners. J R Coll Gen Pract. 1967;13(May):267. 34. Inman WHW, et al. Br Med J. 1968;2(April 27):193. 35. Vessey MP, et al. Br Med J. 1968;2(April 27):199. 36. Vessey MP, et al. Br Med J. 1969;2(June 14):651. 37. Sartwell PE, et al. Am J Epidemiol. 1969;90(Nov):365. 38. Vessey MP, et al. Br Med J. 1970;3(July 18):123. 39. Greene GR, et al. Am J Public Health. 1972;62(May):680. 40. Boston Collaborative Drug Surveillance Programme. Lancet. 1973;1(June 23):1399. 41. Stolley PD, et al. Am J Epidemiol. 1975;102(Sept):197. 42. Vessey MP, et al. J Biosoc Sci. 1976;8(Oct):373. 43. Kay CR. J R Coll Gen Pract. 1978;28(July):393. 44. Petitti DB, et al. Am J Epidemiol. 1978;108(Dec):480. 45. Maguire MG, et al. Am J Epidemiol. 1979;110(Aug):188. 46. Petitti DB, et al. JAMA. 1979;242(Sept 14):1150. 47. Porter JB, et al. Obstet Gynecol. 1982;59(March):299. 48. Porter JB, et al. Obstet Gynecol. 1985;66(July):1. 49. Vessey MP, et al. Br Med J. 1986;292(Feb 22):526. 50. Hoover R, et al. Am J Public Health. 1978;68(April):335. 51. Vessey MP. Br J Fam Plann. 1980;6(Oct suppl):1. 52. Collaborative Group for the Study of Stroke in Young Women. N Engl J Med. 1973;288(April 26):871. 53. Royal College of General Practitioners. Oral Contraceptives and Health. New York, NY: Pitman Publ Corp; May 1974. 54. Collaborative Group for the Study of Stroke in Young Women. JAMA. 1975;231(Feb 17):718. 55. Beral V. Lancet. 1976;2(Nov 13):1047. 56. Vessey MP, et al. Lancet. 1977;2(Oct 8):731; and 1981;1(March 7):549. 57. Petitti DB, et al. Lancet. 1978;2(July 29):234. 58. Inman WHW. Br Med J. 1979;2(Dec 8):1468. 59. Vessey MP, et al. Br Med J. 1984;289(Sept 1):530. 60. Inman WHW, et al. Br Med J. 1970;2(April 25):203. 61. Meade TW, et al. Br Med J. 1980;280(May 10):1157. 62. Böttiger LE, et al. Lancet. 1980;1(May 24):1097. 63. Kay CR. Am J Obstet Gynecol. 1982;142(March 15):762. 64. Vessey MP, et al. Br Med J. 1986;292(Feb 22):526. 65. Gordon T, et al. Am J Med. 1977;62(May):707. 66. Beral V, et al. Lancet. 1977;2(Oct 8):727. 67. Ory H. Fam Plann Perspect. 1983;15(March-April):57. 68. Arthes FG, et al. Cancer. 1971;28(Dec):1391. 69. Vessey MP, et al. Br Med J. 1972;3(Sept 23):719. 70. Boston Collaborative Drug Surveillance Program. N Engl J Med. 1974;290(Jan 3):15. 71. Vessey MP, et al. Lancet. 1975;1(April 26):941. 72. Casagrande J, et al. J Natl Cancer Inst. 1976;56(April):839. 73. Kelsey JL, et al. Am J Epidemiol. 1978;107(March):236. 74. Kay CR. Br Med J. 1981;282(June 27):2089. 75. Vessey MP, et al. Br Med J. 1981;282(June 27):2093. 76. The Cancer and Steroid Hormone Study of the Centers for Disease Control and the National Institute of Child Health and Human Development. Oral contraceptive use and the risk of breast cancer. N Engl J Med. 1986;315(Aug 14):405. 77. Paul C, et al. Br Med J. 1986;293(Sept 20):723. 78. Miller DR, et al. Obstet Gynecol. 1986;68(Dec):863. 79. Pike MC, et al. Lancet. 1983;2(Oct 22):926. 80. McPherson K, et al. Br J Cancer. 1987;56(Nov):653. 81. Hoover R, et al. N Engl J Med. 1976;295(Aug 19):401. 82. Lees AW, et al. Int J Cancer. 1978;22(Dec):700. 83. Brinton LA, et al. J Natl Cancer Inst. 1979;62(Jan):37. 84. Black MM. Pathol Res Pract. 1980;166:491; and Cancer. 1980;46(Dec):2747; and Cancer. 1983;51(June):2147. 85. Clavel F, et al. Bull Cancer (Paris). 1981;68(Dec):449. 86. Brinton LA, et al. Int J Epidemiol. 1982;11(Dec):316. 87. Harris NV, et al. Am J Epidemiol. 1982;116(Oct):643. 88. Jick H, et al. Am J Epidemiol. 1980;112(Nov):577. 89. McPherson K, et al. Lancet. 1983;2(Dec 17):1414. 90. Hoover R, et al. J Natl Cancer Inst. 1981;67(Oct):815. 91. Jick H, et al. Am J Epidemiol. 1980;112(Nov):586. 92. Meirik O, et al. Lancet. 1986;2(Sept 20):650. 93. Fasal E, et al. J Natl Cancer Inst. 1975;55(Oct):767. 94. Paffenbarger RS, et al. Cancer. 1977;39(April suppl): 1887. 95. Stadel BV, et al. Contraception. 1988;38(Sept):287. 96. Miller DR, et al. Am J Epidemiol. 1989;129(Feb):269. 97. Kay CR, et al. Br J Cancer. 1988;58(Nov):675. 98. Miller DR, et al. Obstet Gynecol. 1986;68(Dec):863. 99. Olsson H, et al. Lancet. 1985;1(March 30):748. 100. Chilvers C, et al. Lancet. 1989;1(May 6):973. 101. Huggins GR, et al. Fertil Steril. 1987;47(May):733. 102. Pike MC, et al. Br J Cancer. 1981;43(Jan):72. 103. Ory H, et al. Am J Obstet Gynecol. 1976;124(March 15): 573. 104. Stern E, et al. Science. 1977;196(June 24):1460. 105. Peritz E, et al. Am J Epidemiol. 1977;106(Dec):462. 106. Ory HW, et al. In: Garattini S, Berendes H, eds. Pharmacology of Steroid Contraceptive Drugs. New York, NY: Raven Press; 1977:211-224. 107. Meisels A, et al. Cancer. 1977;40(Dec):3076. 108. Goldacre MJ, et al. Br Med J. 1978;1(March 25):748. 109. Swan SH, et al. Am J Obstet Gynecol. 1981;139(Jan 1):52. 110. Vessey MP, et al. Lancet. 1983;2(Oct 22):930. 111. Dallenbach-Hellweg G. Pathol Res Pract. 1984;179:38. 112. Thomas DB, et al. Br Med J. 1985;290(March 30):961. 113. Brinton LA, et al. Int J Cancer. 1986;38(Sept):339. 114. Ebeling K, et al. Int J Cancer. 1987;39(April):427. 115. Beral V, et al. Lancet. 1988;2(Dec 10):1331. 116. Baum JK, et al. Lancet. 1973;2(Oct 27):926. 117. Edmondson HA, et al. N Engl J Med. 1976;294(Feb 26): 470. 118. Bein NN, et al. Br J Surg. 1977;64(June):433. 119. Klatskin G. Gastroenterology. 1977;73(Aug):386. 120. Rooks JB, et al. JAMA. 1979;242(Aug 17):644. 121. Sturtevant FM. In: Moghissi K, ed. Controversies in Contraception, Baltimore, MD; Williams & Wilkins; 1979:93-150. 122. Henderson BE, et al. Br J Cancer. 1983;48(July):437. 123. Neuberger J, et al. Br Med J. 1986;292(May 24):1355. 124. Forman D, et al. Br Med J. 1986;292(May 24):1357. 125. La Vecchia C, et al. Br J Cancer. 1989;59(March):460. 126. Savolainen E, et al. Am J Obstet Gynecol. 1981;140(July 1):521. 127. Ferencz C, et al. Teratology. 1980;21(April):225. 128. Rothman KJ, et al. Am J Epidemiol. 1979;109(April):433. 129. Harlap S, et al. Obstet Gynecol. 1980;55(April):447. 130. Layde PM, et al. J Epidemiol Community Health. 1982;36(Dec)274. 131. Rome Group for the Epidemiology and Prevention of Cholelithiasis (GREPCO). Am J Epidemiol. 1984;119(May):796. 132. Strom BL, et al. Clin Pharmacol Ther. 1986;39(March):335. 133. Wynn V. In: Bardin CE, et al, eds. Progesterone and Progestins. New York, NY: Raven Press; 1983:395-410. 134. Perlman JA, et al. J Chron Dis. 1985;38(Oct):857. 135. Powell MG, et al. Obstet Gynecol. 1984;63(June):764. 136. Wynn V, et al. Lancet. 1966;2(Oct 1):720. 137. Fisch IR, et al. JAMA. 1977;237(June 6):2499. 138. Kay CR. Lancet. 1977;1(March 19):624. 139. Laragh JH. Am J Obstet Gynecol. 1976;126(Sept 1):141. 140. Ramcharan S. In: Garattini S, Berendes HW, eds. Pharmacology of Steroid Contraceptive Drugs. New York, NY: Raven Press; 1977:277-288. 141. Laumas KR, et al. Am J Obstet Gynecol. 1967;98(June 1): 411. 142. Saxena BN, et al. Contraception. 1977;16(Dec):605. 143. Nilsson S, et al. Contraception. 1978;17(Feb):131. 144. Washington AE, et al. JAMA. 1985;253(April 19):2246. 145. Louv WC, et al. Am J Obstet Gynecol. 1989;160(Feb):396. 146. Francis WG, et al. Can Med Assoc J. 1965;92 (Jan 23):191. 147. Verhulst HL, et al. J Clin Pharmacol. 1967:7 (Jan-Feb):9. 148. Ory HW. Fam Plann Perspect. 1982;14 (July-Aug):182. 149. Ory HW, et al. Making Choices: Evaluating the Health Risks and Benefits of Birth Control Methods. New York, NY: The Alan Guttmacher Institute; 1983. 150. Palmer JR, et al. Am J Epidemiol. 1989;130 (Nov):878. 151. Romieu I, et al. J Natl Cancer Inst. 1989;81 (Sept): 1313. 152. Porter JB, et al. Obstet Gynecol. 1987;70 (July):29.


BRIEF SUMMARY OF PATIENT WARNINGS

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

Cigarette smoking increases the risk of serious adverse effects on the heart and blood vessels from oral contraceptive use. This risk increases with age and with heavy smoking (15 or more cigarettes per day) and is quite marked in women over 35 years of age. Women who use oral contraceptives are strongly advised not to smoke.

In the detailed leaflet, "What You Should Know About Oral Contraceptives," which you have received, the risks and benefits of oral contraceptives are discussed in much more detail. That leaflet also provides information on other forms of contraception. Please take time to read it carefully for it may have been recently revised.

If you have any questions or problems regarding this information, contact your doctor.

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. However, forgetting to take pills considerably increases the chances of pregnancy.

For most women, oral contraceptives are free of serious or unpleasant side effects. However, oral contraceptive use is associated with certain serious diseases or conditions that can cause severe disability or death, though rarely. 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:

Women should not use oral contraceptives if they suspect they are pregnant or if they have unexplained vaginal bleeding.

Most side effects of the pill are not serious. The most common 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 three months of use.

Proper use of oral contraceptives requires that they be taken under your doctor's continuing supervision, because they can be associated with serious side effects. 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, and that certain of the risks may persist after use of the pill has been discontinued:

  1. Blood clots in the legs, arms, lungs, heart (heart attack), eyes, abdomen, or elsewhere in the body. As mentioned above, smoking increases the risk of heart attacks and strokes and subsequent serious medical consequences.
  2. Stroke, due to a blood clot, or to bleeding in the brain (hemorrhage) as a result of bursting of a blood vessel. Stroke can lead to paralysis in all or part of the body, or to death.
  3. Liver tumors, which may rupture and cause severe bleeding and death. A possible, but not definite, association has also been found with the pill and liver cancer. However, with or without use of the pill, liver cancers are extremely rare in the United States.
  4. High blood pressure, although blood pressure ordinarily, but not always, returns to original levels when the pill is stopped.
  5. Gallbladder disease, which might require surgery.

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, you should be aware that drugs such as antiepileptics, antibiotics (especially rifampin), as well as certain other drugs, may decrease oral contraceptive effectiveness.

There is a conflict among studies regarding breast cancer and oral contraceptive use. 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. The majority of studies have found no overall increase in the risk of developing breast cancer. 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. There is insufficient evidence to rule out the possibility that pills may cause such cancers.

Taking the pill may provide some important non-contraceptive benefits. These include less painful menstruation, less menstrual blood loss and anemia, less risk of fibroids, pelvic infections, and noncancerous breast diseases, and less risk of cancer of the ovary and of the lining of the uterus (womb).

Be sure to discuss any medical condition you may have with your health care provider. He or she will take a medical and family history before prescribing oral contraceptives and will also 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 that you should read and discuss with your health care provider.


DETAILED PATIENT LABELING:
WHAT YOU SHOULD KNOW ABOUT ORAL CONTRACEPTIVES

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

It is important that any woman who considers using an oral contraceptive understand the risks involved. Although the oral contraceptives have important advantages over other methods of contraception, they have certain risks that no other method has. Only you and your physician can decide whether the advantages are worth these risks. This leaflet will tell you about the most important risks. It will explain how you can help your doctor prescribe the pill as safely as possible by telling him/her about yourself and being alert for the earliest signs of trouble. And it will tell you how to use the pill properly so that it will be as effective as possible. THERE IS MORE DETAILED INFORMATION AVAILABLE IN THE LEAFLET PREPARED FOR DOCTORS. Your pharmacist can show you a copy or you can request one from the manufacturer by phoning toll-free 1-800-323-4204; you may need your doctor's help in understanding parts of it.

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 revisits. You should also follow your doctor's advice with regard to regular check-ups while you are on the pill.

If you do not have any of the conditions listed below and are thinking about using oral contraceptives, to help you decide, you need information about the advantages and risks of oral contraceptives and of other contraceptive methods as well. This leaflet describes the advantages and risks of oral contraceptives. Except for sterilization, the intrauterine device (IUD), and abortion, which have their own specific risks, the only risks of other methods are those due to pregnancy should the method fail. Your doctor can answer questions you may have with respect to other methods of contraception, and further questions you may have on oral contraceptives after reading this leaflet.


WHAT ARE ORAL CONTRACEPTIVES?

The most common type of oral contraceptive, often simply called "the pill," is a combination of estrogen and progestogen, the two kinds of female hormones. The amount of estrogen and progestogen can vary, but the amount of estrogen is more important because both the effectiveness and some of the dangers of the pill have been related to the amount of estrogen. The pill works principally by preventing release of an egg from the ovary during the cycle in which the pills are taken.


EFFECTIVENESS OF ORAL CONTRACEPTIVES

The pill is one of the most effective 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) when used perfectly, without missing any pills. Typical failure rates are actually about 3% per year. The chance of becoming pregnant increases with each missed pill during a menstrual cycle.

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


WHO SHOULD NOT TAKE ORAL CONTRACEPTIVES

Cigarette smoking increases the risk of serious adverse effects on the heart and blood vessels from oral contraceptive use. This risk increases with age and with heavy smoking (15 or more cigarettes per day) and is quite marked in women over 35 years of age. Women who use oral contraceptives are strongly advised not to smoke.

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 should also not use the pill if you have any of the following conditions:

Tell your health care provider if you have ever had any of these conditions. He or she 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 any of the following conditions, as he or she will want to watch them closely or they might cause him or her to suggest using another method of contraception:

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 tell your doctor 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 3 to 4 weeks before surgery and not taking oral contraceptives for 2 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 4 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 also the section on Breast feeding in General Precautions.)

The risk of circulatory disease in oral contraceptive users may be higher in users of high-dose pills and may be greater with longer duration of oral contraceptive use. In addition, some of these increased risks may continue for a number of years after stopping oral contraceptives. The risk of abnormal blood clotting increases with age in both users and nonusers of oral contraceptives, but the increased risk from the oral contraceptive appears to be present at all ages. For women aged 20 to 44 it is estimated that about 1 in 2,000 using oral contraceptives will be hospitalized each year because of abnormal clotting. Among nonusers in the same age group, about 1 in 20,000 would be hospitalized each year. For oral contraceptive users in general, it has been estimated that in women between the ages of 15 and 34, the risk of death due to a circulatory disorder is about 1 in 12,000 per year, whereas for nonusers the rate is about 1 in 50,000 per year. In the age group 35 to 44, the risk is estimated to be about 1 in 2,500 per year for oral contraceptive users and about 1 in 10,000 per year for nonusers.

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

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

3. Gallbladder disease. Oral contraceptive users probably have a greater risk than nonusers of having gallbladder disease, although this risk may be related to pills containing high doses of estrogens.

4. Liver tumors. In rare cases, oral contraceptives can cause benign but dangerous liver tumors. These benign 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 several 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 rare.

5. Cancer of the reproductive organs and breasts. There is conflict among studies regarding breast cancer and oral contraceptive use. 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. The majority of studies have found no overall increase in the risk of developing breast cancer.

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. There is insufficient evidence to rule out the possibility that pills may cause such cancers.


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 that 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.

Annual number of birth-related or method-related deaths associated with control of fertility per 100,000 nonsterile women, by fertility control method according to age.
Age
Method of control 15-19 20-24 25-29 30-34 35-39 40-44
No fertility control methods* 7.0 7.4 9.1 14.8 25.7 28.2
Oral contraceptives
nonsmoker** 0.3 0.5 0.9 1.9 13.8 31.6
smoker** 2.2 3.4 6.6 13.5 51.1 117.2
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 in the table that for women aged 15 to 39, the risk of death was highest with pregnancy (7-26 deaths per 100,000 women, depending on age). Among pill users who do not smoke, the risk of death was 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 four times higher (117/100,000 women) than the estimated risk associated with pregnancy (28/100,000) 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, nonsmoking 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:


SIDE EFFECTS OF ORAL CONTRACEPTIVES

1. Vaginal bleeding.

Spotting. This is a slight staining between your menstrual periods that may not even require a pad. Some women spot even though they take their pills exactly as directed. Many women spot although they have never taken the pills. Spotting does not mean that your ovaries are releasing an egg. Spotting may be the result of irregular pill-taking. Getting back on schedule will usually stop it.

If you should spot while taking the pills, you should not be alarmed, because spotting usually stops by itself within a few days. It seldom occurs after the first pill cycle. Consult your doctor if spotting persists for more than a few days or if it occurs after the second cycle.

Unexpected (breakthrough) bleeding. Unexpected (breakthrough) bleeding does not mean that your ovaries have released an egg. It seldom occurs, but when it does happen it is most common in the first pill cycle. It is a flow much like a regular period, requiring the use of a pad or tampon.

If you experience breakthrough bleeding use a pad or tampon and continue with your schedule. Usually your periods will become regular within a few cycles. Breakthrough bleeding will seldom bother you again.

Consult your doctor if breakthrough bleeding is heavy, does not stop within a week, or if it occurs after the second cycle.

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 or raised blood pressure. Oral contraceptives may cause edema (fluid retention), with swelling of the fingers or ankles. If you experience fluid retention, contact your doctor or health care provider. Some women develop high blood pressure while on the pill, which ordinarily, but not always, returns to the original levels when the pill is stopped. High blood pressure predisposes one to strokes, heart attacks, kidney disease, and other diseases of the blood vessels.

4. Melasma. A spotty darkening of the skin is possible, particularly of the face. This may persist after the pill is discontinued.

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

If any of these, or other, side effects occur, call your doctor or health care provider.


GENERAL PRECAUTIONS

1. Missed periods and use of oral contraceptives before or during early pregnancy. Occasionally women who are taking the pill miss periods. It has been reported to occur as frequently as several times each year in some women, depending on various factors such as age and prior history. (Your doctor is the best source of information about this.) The pill should not be used when you are pregnant or suspect you may be pregnant. Very rarely, women who are using the pill as directed become pregnant. The likelihood of becoming pregnant is higher if you occasionally miss one or two pills. Therefore, if you miss a period you should consult your physician before continuing to take the pill. If you miss a period, especially if you have not taken the pill regularly, you should use an alternative method of contraception until pregnancy has been ruled out; if you have missed more than one pill at any time, you should immediately start using an additional method of contraception and complete your pill cycle.

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 findings have not been seen in more recent studies. 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 of any medication taken during pregnancy.

2. Breast feeding. 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 while breast feeding. You should use another method of contraception since breast feeding provides only partial protection from becoming pregnant and this partial protection decreases significantly as you breast feed for longer periods of time. 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), and possibly certain antibiotics. You may need to use additional contraception when you take drugs that can make oral contraceptives less effective.

Oral contraceptives may have an influence upon the way other drugs act. Check with your doctor if you are taking any other drugs while you are on the pill.


HOW TO TAKE ORAL CONTRACEPTIVES

1. General instructions. You must take your pill every day according to the instructions. Oral contraceptives are most effective if taken 24 hours apart. Take your pill at the same time every day so that you are less likely to forget to take it. You will then maintain an effective dose of the oral contraceptive in your body.

When you first begin to use the pill, you should use an additional method of protection until you have taken your first 7 pills if you are using the Sunday start schedule.

To remove a pill, press down on it. The pill will drop through a hole in the bottom of the Compack.

The two "three weeks on — one week off" schedules. Your Demulen 1/35-21 or Demulen 1/50-21 Compack contains 21 tablets arranged in three numbered rows with the days of the week printed above them.

Day-1 schedule. If you are to begin on day 1, count the day you start to menstruate as day 1 and begin taking your pills that same day. Start in row #1 with the pill under the day that corresponds to the day that your flow began. Continue to take one pill each day on consecutive days of the week.

After the last (Saturday) pill in row #3 has been taken, if any remain in the first row, complete your 21-pill schedule by taking one pill daily starting with Sunday in row #1. Then stop for 1 week before starting to take the pills again. Begin your next pill cycle on the same day of the week that you began the first cycle.

Sunday schedule. Start taking the pills on the first Sunday after your period begins unless your period begins on Sunday. If your period begins on Sunday start taking the pill that very same day.

Begin in row #1 and take your pills, one each day on consecutive days, for 3 weeks (21 days), then stop taking them for 1 week (7 days) before starting to take the pills again on Sunday.

Whether you begin on "day 1" or on Sunday, continue taking your pills as directed, month after month, regardless of whether your flow has or has not ceased, whether you may have experienced spotting or unexpected (breakthrough) bleeding, or whether you feel sick to your stomach during your pill cycle. You will probably have your period about every 28 days.

The "pill-a-day" schedule. Your Demulen 1/35-28 or Demulen 1/50-28 Compack contains 28 pills arranged in four numbered rows of 7 pills each with the days of the week printed above them.

You must take your pills in order, one pill each day. Begin with the Sunday pill in row #1.

1 — Start taking the pills on the first Sunday after your period begins unless your period begins on Sunday. If your period begins on Sunday start taking the pills that very same day.

2 — Continue to take one pill each day on consecutive days of the week.

3 — After the Saturday pill in row #1 has been taken begin taking pills in row #2, and so on, until the Saturday pill in row #4 has been taken.

4 — Begin a new pill cycle the next day, starting with the Sunday pill in row #1.

You will probably have your period about every 28 days, while you are taking the blue (pink for Demulen 1/50-28) pills.

Continue your pill-a-day schedule, month after month, regardless of whether your flow ceases while you are taking the colored pills, whether you experience spotting or unexpected (breakthrough) bleeding, or whether you feel sick to your stomach during a cycle.

Take your pill faithfully every "pill day"!

It is important that you take a pill without fail every pill day, at intervals of 24 hours, for two reasons: First, your ovaries may release an egg and therefore you may become pregnant if you do not take your pills regularly. Second, you may spot or start to flow between your periods. This may be inconvenient.

Take your pill at the same time every day!

You are probably wondering why the same time of day is important. By taking your pill at the same time every day it becomes a good habit, and you are much less likely to forget. You may wish to keep your pills in the medicine cabinet near your toothbrush as a reminder to take them when you brush your teeth at night. The best time to take your daily pill may be at bedtime. You may find it helpful to associate your pill-taking with something else you do every day at a particular time.

Another very important reason for you to take your pills as "regular as clockwork" is that you are protected best when you take one every 24 hours; they are made to work that way. Just remember that once every day is not the same as once every 24 hours. Here is why: Suppose you were to take your Monday pill in the morning when you get up, and then not take your Tuesday pill till the evening before you go to bed. True, you will have taken a pill each day, on Monday and on Tuesday — but the time between pill-taking will probably have been more than 36 hours, or more than 1-1/2; days! You might spot. Chances are you would still be protected and would not get pregnant, but why risk it when it is so easy to guarantee yourself maximal protection by taking your pill faithfully every pill day and at the same time every pill day?

If you are scheduled for surgery, or you need prolonged bed rest, you should tell your doctor that you are on the pill and stop taking the pill 4 weeks before surgery to avoid an increased risk of blood clots. It is also advisable not to start oral contraceptives sooner than 4 weeks after delivery of a baby.

2. If you forget to take your pill. If you miss only one white (active) pill in a cycle, the chance of becoming pregnant is small. Take the missed pill as soon as you realize that you have forgotten it and continue to take your tablets for the rest of that cycle as directed. Since the risk of pregnancy increases with each additional pill you skip, it is very important that you take one pill a day.

If you forget your pills (except for the inactive colored pills in Demulen 1/35-28 or Demulen 1/50-28) on 2 consecutive days in week 1 or 2 of the pack, do not be surprised if you spot or start to flow. You should take two pills each day for the next 2 days. 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 backup for those 7 days.

If you forget two consecutive active pills in week 3 of the pack or if you forget three consecutive active pills in any of the first 3 weeks of the pack, do one of the following: Day 1 Starters should discard the rest of the pack and begin a new pack that same day; Sunday Starters should continue to take 1 pill daily until Sunday, discard the rest of the pack, and begin a new pack that same day. You may not have a 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. You may become pregnant if you have sex in the 7 days after you miss pills. You must use another method of birth control as a backup for those 7 days.

If you are using Demulen 1/35-28 or Demulen 1/50-28 and forget to take one or more colored pills, begin a new cycle on the next Sunday; use a new package and start taking the white pills. Missing the colored pills does not increase your chances of getting pregnant providing the white pill schedule has been followed.

3. Pregnancy due to pill failure. The incidence of pill failure resulting in pregnancy is approximately 1% (ie, one pregnancy per 100 women per year) if taken every day as directed, but, because some women fail to follow the daily schedule, more typical failure rates are about 3%. If you become pregnant, you should discuss your pregnancy with your doctor.

4. Pregnancy after stopping the pill. There may be some delay in becoming pregnant after you stop using oral contraceptives, especially if you had irregular menstrual cycles before you used oral contraceptives. It may be advisable to postpone conception until you begin menstruating regularly once you have stopped taking the pill and desire pregnancy.

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

5. Overdosage. Serious ill effects have not been reported following ingestion of large doses of oral contraceptives by young children. Overdosage may cause nausea and withdrawal bleeding in females. In case of overdosage, contact your health care provider, pharmacist, or Poison Control Center.

6. Other information. Your doctor will take a medical and family history before prescribing oral contraceptives and will also 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. Certain health problems or conditions in your medical or family history may require that your doctor see you more frequently while you are taking the pill. Be sure to keep all appointments with your health care provider because this is a time to determine if there are early signs of side effects of oral contraceptive use.

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

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.


HEALTH BENEFITS FROM ORAL CONTRACEPTIVES

In addition to preventing pregnancy, use of oral contraceptives may provide certain benefits. They are:

If you want more information about birth control pills, ask your doctor or pharmacist. They have a more technical leaflet called the Professional Labeling, which you may wish to read. The Professional Labeling is also published in a book entitled Physicians' Desk Reference, available in many book stores and public libraries.

Be certain to read new revisions of this leaflet. You may check the date of the most recent revision by phoning the manufacturer toll-free at 1-800-323-4204 or by writing to the address below.

7/15/97

G.D. Searle & Co.
Chicago IL 60680 USA

©1997, G.D. Searle & Co.


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