Yasmin® 28 Tablets
(drospirenone and ethinyl estradiol)
PATIENTS SHOULD BE COUNSELED THAT THIS PRODUCT DOES NOT PROTECT AGAINST HIV INFECTION (AIDS) AND OTHER SEXUALLY TRANSMITTED DISEASES
YASMIN provides an oral contraceptive regimen consisting of 21 active film coated tablets each containing 3.0 mg of drospirenone and 0.030 mg of ethinyl estradiol and 7 inert film coated tablets. The inactive ingredients are lactose monohydrate NF, corn starch NF, modified starch NF, povidone 25000 USP, magnesium stearate NF, hydroxylpropylmethyl cellulose USP, macrogol 6000 NF, talc USP, titanium dioxide USP, ferric oxide pigment, yellow NF. The inert film coated tablets contain lactose monohydrate NF, corn starch NF, povidone 25000 USP, magnesium stearate NF, hydroxylpropylmethyl cellulose USP, talc USP, titanium dioxide USP.
Drospirenone (6R,7R,8R,9S,10R,13S,14S,15S,16S,17S)-1,3',4',6,6a,7,8,9,10,11, 12,13,14,15,15a,16-hexadecahydro-10,13-dimethylspiro-[17H-dicyclopropa-6,7:15,16]cyclopenta[a]phenanthrene-17,2'(5H)-furan]-3,5'(2H)-dione) is a synthetic progestational compound and has a molecular weight of 366.5 and a molecular formula of C24H30O3. Ethinyl estradiol (19-nor-17α-pregna 1,3,5(10)-triene-20-yne-3,17-diol) is a synthetic estrogenic compound and has a molecular weight of 296.4 and a molecular formula of C20H24O2. The structural formulas are as follows:
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Last updated on RxList: 7/10/2007
YASMIN is indicated for the prevention of pregnancy in women who elect to use an oral contraceptive.
Oral contraceptives are highly effective. Table II 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, depends upon the reliability with which they are used. Correct and consistent use of methods can result in lower failure rates.
TABLE II.
Percentage of women experiencing a unintended pregnancy during the first year
of typical use and first year of perfect use of contraception and the percentage
continuing use at the end of the first year: United States.
| % of Women Experiencing an Accidental Pregnancy with in the First Year of Use | % of Women Continuing Use at One Year3 | ||
| Method (1) | Typical Use1 (2) | Perfect Use2 (3) | (4) |
| Chance4 | 85 | 85 | |
| Spermicides5 | 26 | 6 | 40 |
| Periodic abstinence | 25 | 63 | |
| Calendar | 9 | ||
| Ovulation method | 3 | ||
| Sympto-thermal6 | 2 | ||
| Post-ovulation | 1 | ||
| Withdrawal | 19 | 4 | |
| Cap7 | |||
| Parous women | 40 | 26 | 42 |
| Nulliparous women | 20 | 9 | 56 |
| Sponge | |||
| Parous women | 40 | 20 | 42 |
| Nulliparous women | 20 | 9 | 56 |
| Diaphragm7 | 20 | 6 | 56 |
| Condom8 | |||
| Female (Reality) | 21 | 5 | 56 |
| Male | 14 | 3 | 61 |
| Pill | 5 | 71 | |
| progestin only | 0.5 | ||
| combined | 0.1 | ||
| IUD: | |||
| Progesterone T: | 2.0 | 1.5 | 81 |
| Copper T 380A | 0.8 | 0.6 | 78 |
| Lng 20 | 0.1 | 0.1 | 81 |
| Depo Provera | 0.3 | 0.3 | 70 |
| Norplant and Norplant-2 | 0.05 | 0.05 | 88 |
| Female sterilization | 0.5 | 0.5 | 100 |
| Male sterilization | 0.15 | 0.10 | 100 |
| Emergency Contraceptive Pills: Treatment initiated
within 72 hours after unprotected intercourse reduces the risk of pregnancy
by at least 75%.9 Lactational Amenorrhea Method: LAM is highly effective, temporary method of contraception.10 Source: Trussell J, Contraceptive efficacy. In Hatcher RA, Trussell J, Stewart F, Cates W, Stewart GK, Kowal D, Guest F, Contraceptive Technology: Seventeenth Revised Edition. New York NY: Irvington Publishers, 1998. 1 Among typical couples who initiate use of a method (not necessarily for the first time), the percentage who experience an accidental pregnancy during the first year if they do not stop use for any other reason. 2 Among couples who initiate use of a method (not necessarily for the first time) and who use it perfectly (both consistently and correctly). the percentage who experience an accidental pregnancy during the first year if they do not stop use for any reason. 3 Among couples attempting to avoid pregnancy, the percentage who continue to use a method for one year. 4 The percents becoming pregnant in columns (2) and (3) are based on data from populations where contraception is not used and from women who cease using contraception in order to become pregnant. Among such populations, about 89% become pregnant within one year. This estimate was lowered slightly (to 85%) to represent the percentage who would become pregnant within one year among women now relying on reversible methods of contraception if they abandoned contraception altogether. 5 Foams, creams, gels vaginal suppositories, and vaginal film. 6 Cervical mucus (ovulation) method supplemented by calendar in the pre-ovulatory and basal body temperature in the post-ovulatory phases. 7 With spermicidal cream or jelly 8 Without spermicides. 9 The treatment schedule is one dose within 72 hours after unprotected intercourse, and a second dose 12 hours after the first dose. The Food and Drug Administration has declared the following brands of oral contraceptives to be safe and effective for emergency contraception: Ovral (1 dose is 2 white pills), Alesse (1 dose is 5 pink pills), Nordette or Levlen (1 dose is 2 light-orange pills), Lo/Ovral (1 dose is 4 white pills), Triphasil or Tri-Levlen (1 dose is 4 yellow pills). 10 However, to maintain effective protection against pregnancy, another method of contraception must be used as soon as menstruation resumes, the frequency or duration of breastfeeds is reduced, bottle feeds are introduced, or the baby reaches six months of age. |
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In clinical efficacy studies of YASMIN of up to 2 years duration, 2,629 subjects completed 33,160 cycles of use without any other contraception. The mean age of the subjects was 25.5 ± 4.7 years. The age range was 16 to 37 years. The racial demographic was: 83 % Caucasians, 1 % Hispanic, 1% Black, < 1% Asian, < 1% other, < 1% missing data, 14% not inquired and < 1% unspecified. Pregnancy rates in the clinical trials were less than one per 100 woman-years of use.
To achieve maximum contraceptive effectiveness, YASMIN (drospirenone and ethinyl estradiol) must be taken exactly as directed at intervals not exceeding 24-hours.
YASMIN consists of 21 tablets of a monophasic combined hormonal preparation plus 7 inert tablets. The dosage of YASMIN is one yellow tablet daily for 21 consecutive days followed by 7 white inert tablets per menstrual cycle. A patient should begin to take YASMIN either on the first day of her menstrual period (Day 1 Start) or on the first Sunday after the onset of her menstrual period (Sunday Start).
Day 1 Start. During the first cycle of YASMIN use, the patient should be instructed to take one yellow YASMIN daily, beginning on day one (1) of her menstrual cycle. (The first day of menstruation is day one.) She should take one yellow YASMIN daily for 21 consecutive days, followed by one white inert tablet daily on menstrual cycle days 22 through 28. It is recommended that YASMIN be taken at the same time each day, preferably after the evening meal or at bedtime. If YASMIN is first taken later than the first day of the menstrual cycle, YASMIN should not be considered effective as a contraceptive until after the first 7 consecutive days of product administration. The possibility of ovulation and conception prior to initiation of medication should be considered.
Sunday Start. During the first cycle of YASMIN use, the patient should be instructed to begin to take one yellow YASMIN daily, beginning on the first Sunday after the onset of her menstrual period. She should take one yellow YASMIN daily for 21 consecutive days, followed by one white inert tablet daily on menstrual cycle days 22 through 28. It is recommended that YASMIN be taken at the same time each day, preferably after the evening meal or at bedtime. YASMIN should not be considered effective as a contraceptive until after the first 7 consecutive days of product administration. The possibility of ovulation and conception prior to initiation of medication should be considered.
The patient should begin her next and all subsequent 28-day regimens of YASMIN on the same day of the week that she began her first regimen, following the same schedule. She should begin taking her yellow tablets on the next day after ingestion of the last white tablet, regardless of whether or not a menstrual period has occurred or is still in progress. Anytime a subsequent cycle of YASMIN is started later than the day following administration of the last white tablet, the patient should use another method of contraception until she has taken a yellow YASMIN daily for seven consecutive days.
When switching from another oral contraceptive, YASMIN should be started on the same day that a new pack of the previous oral contraceptive would have been started.
Withdrawal bleeding usually occurs within 3 days following the last yellow tablet. If spotting or breakthrough bleeding occurs while taking YASMIN, the patient should be instructed to continue taking her YASMIN as instructed and by the regimen described above. She should be instructed that this type of bleeding is usually transient and without significance; however, if the bleeding is persistent or prolonged, the patient should be advised to consult her physician.
Although the occurrence of pregnancy is unlikely if YASMIN is taken according to directions, if withdrawal bleeding does not occur, the possibility of pregnancy must be considered. If the patient has not adhered to the prescribed dosing schedule (missed one or more active tablets or started taking them on a day later than she should have), the possibility of pregnancy should be considered at the time of the first missed period and appropriate diagnostic measures taken. If the patient has adhered to the prescribed regimen and misses two consecutive periods, pregnancy should be ruled out. Hormonal contraceptives should be discontinued if pregnancy is confirmed.
The risk of pregnancy increases with each active yellow tablet missed. For additional patient instructions regarding missed pills, see the "WHAT TO DO IF YOU MISS PILLS" section in the DETAILED PATIENT LABELING which follows. If breakthrough bleeding occurs following missed tablets, it will usually be transient and of no consequence. If the patient misses one or more white tablets, she should still be protected against pregnancy provided she begins taking yellow tablets again on the proper day.
In the nonlactating mother, YASMIN may be initiated 4 weeks postpartum, for contraception. When the tablets are administered in the postpartum period, the increased risk of thromboembolic disease associated with the postpartum period must be considered. (See "CONTRAINDICATIONS", "WARNINGS", and "PRECAUTIONS" concerning thromboembolic disease.)
YASMIN 28 Tablets (drospirenone and ethinyl estradiol) are available in packages of 3 BLISTER packs (NDC 50419-402-03).
Each pack contains 21 active yellow round, unscored, film coated tablets each containing 3mg drospirenone and 0.03mg ethinyl estradiol, and 7 inert white round, unscored, film coated tablets.
Store at 25º C (77º F); excursions permitted to 15-30oC (59-86oF) [See USP Controlled Room Temperature].
REFERENCES FURNISHED UPON REQUEST
Manufactured for Berlex Laboratories
Manufactured in Germany
BERLEX® Laboratories, Wayne, NJ 07470
FDA rev date: 5/9/2003
Last updated on RxList: 7/10/2007
An increased risk of the following serious adverse reactions has been associated with the use of oral contraceptives (see "WARNINGS" section).
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 have been reported in users of oral contraceptives and a causal association has been neither confirmed nor refuted:
The following are the most common adverse events reported with use of YASMIN during the clinical trials, occurring in > 1% of subjects and which may or may not be drug related: Headache, Menstrual Disorder, Breast Pain, Abdominal Pain, Nausea, Leukorrhea, Flu Syndrome, Acne, Vaginal Moniliasis, Depression, Diarrhea, Asthenia, Dysmenorrhea, Back Pain, Infection, Pharyngitis, Intermenstrual Bleeding, Migraine, Vomiting, Dizziness, Nervousness, Vaginitis, Sinusitis, Cystitis, Bronchitis, Gastroenteritis, Allergic Reaction, Urinary Tract Infection, Pruritus, Emotional Lability, Surgery, Rash, Upper Respiratory Infection.
Rifampin. Metabolism of ethinyl estradiol and some progestins (e.g., norethindrone) is increased by rifampin. A reduction in contraceptive effectiveness and an increase in menstrual irregularities have been associated with concomitant use of rifampin.
Anticonvulsants. Anticonvulsants such as phenobarbital, phenytoin, and carbamazepine have been shown to increase the metabolism of ethinyl estradiol and/or some progestins, which could result in a reduction of contraceptive effectiveness.
Antibiotics. Pregnancy while taking combined hormonal contraceptives has been reported when the combined hormonal contraceptives were administered with antimicrobials such as ampicillin, tetracycline, and griseofulvin. However, clinical pharmacokinetic studies have not demonstrated any consistent effects of antibiotics (other than rifampin) on plasma concentrations of synthetic steroids.
Atorvastatin: Coadministration of atorvastatin and an oral contraceptive increased AUC values for norethindrone and ethinyl estradiol by approximately 30% and 20%, respectively.
St. John's Wort: Herbal products containing St. John's Wort (hypericum perforatum) may induce hepatic enzymes (cytochrome P450) and p-glycoprotein transporter and may reduce the effectiveness of oral contraceptives and emergency contraceptive pills. This may also result in breakthrough bleeding.
Other: Ascorbic acid and acetaminophen may increase plasma concentrations of some synthetic estrogens, possibly by inhibition of conjugation. A reduction in contraceptive effectiveness and an increased incidence of menstrual irregularities has been suggested with phenylbutazone.
Combined oral contraceptives containing ethinyl estradiol may inhibit the metabolism of other compounds. Increased plasma concentrations of cyclosporine, prednisolone, and theophylline have been reported with concomitant administration of oral contraceptives. In addition, oral contraceptives may induce the conjugation of other compounds. Decreased plasma concentrations of acetaminophen and increased clearance on temazepam, salicylic acid, morphine, and clofibric acid have been noted when these drugs were administered with oral contraceptives.
Certain endocrine- and liver-function tests and blood components may be affected by oral contraceptives:
a. Increased prothrombin and factors VII, VIII, IX and X; decreased antithrombin 3; increased norepinephrine-induced platelet aggregability.
b.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.
c. Other binding proteins may be elevated in serum.
d. Sex-hormone-binding globulins are increased and result in elevated levels of total circulating sex steroids and corticoids; however, free or biologically active levels remain unchanged.
e. Triglycerides may be increased.
f. Glucose tolerance may be decreased.
g. Serum folate levels may be depressed by oral contraceptive therapy. This may be of clinical significance if a woman becomes pregnant shortly after discontinuing oral contraceptives.
Last updated on RxList: 7/10/2007
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.
YASMIN contains 3 mg of the progestin drospirenone that has antimineralocorticoid activity, including the potential for hyperkalemia in high-risk patients, comparable to a 25 mg dose of spironolactone. YASMIN should not be used in patients with conditions that predispose to hyperkalemia (i.e. renal insufficiency, hepatic dysfunction and adrenal insufficiency). Women receiving daily, long-term treatment for chronic conditions or diseases with medications that may increase serum potassium, should have their serum potassium level checked during the first treatment cycle. Drugs that may increase serum potassium include ACE inhibitors, angiotensin - II receptor antagonists, potassium-sparing diuretics, heparin, aldosterone antagonists, and NSAIDs.
The use of oral contraceptives is associated with increased risks of several serious conditions including myocardial infarction, thromboembolism, stroke, hepatic neoplasia, gallbladder disease, and hypertension, although the risk of serious morbidity or mortality is very small in healthy women without underlying risk factors. The risk of morbidity and mortality increases significantly in the presence of other underlying risk factors such as hypertension, hyperlipidemias, obesity and diabetes.
Practitioners prescribing oral contraceptives should be familiar with the following information relating to these risks.
The information contained in this package insert is based principally on studies carried out in patients who used oral contraceptives with higher formulations of estrogens and progestogens than those in common use today. The effect of long-term use of the oral contraceptives with lower formulations of both estrogens and progestogens remains to be determined.
Throughout this labeling, epidemiologic studies reported are of two types: retrospective or case control studies and prospective or cohort studies. Case control studies provide a measure of the relative risk of a disease, namely, a ratio of the incidence of a disease among oral contraceptive users to that among nonusers. The relative risk does not provide information on the actual clinical occurrence of a disease. Cohort studies provide a measure of attributable risk, which is the difference in the incidence of disease between oral contraceptive users and nonusers. The attributable risk does provide information about the actual occurrence of a disease in the population. For further information, the reader is referred to a text on epidemiologic methods.
An increased risk of myocardial infarction has been attributed to oral contraceptive use. This risk is primarily in smokers or women with other underlying risk factors for coronary-artery disease such as hypertension, hypercholesterolemia, morbid obesity, and diabetes. The relative risk of heart attack for current oral contraceptive users has been estimated to be two to six. The risk is very low under the age of 30.
Smoking in combination with oral contraceptive use has been shown to contribute substantially to the incidence of myocardial infarctions in women in their mid-thirties or older with smoking accounting for the majority of excess cases. Mortality rates associated with circulatory disease have been shown to increase substantially in smokers over the age of 35 and nonsmokers over the age of 40 (Table III) among women who use oral contraceptives.
Table III. (Adapted from P.M. Layde and V. Beral)
CIRCULATORY DISEASE MORTALITY RATES PER 100,000 WOMAN-YEARS BY AGE SMOKING STATUS
AND ORAL CONTRACEPTIVE USE
| AGE | EVER-USERS NON-SMOKERS | EVER-USERS SMOKERS | CONTROLS NON-SMOKERS | CONTROL SMOKERS |
| 15-24 | 0.0 | 10.5 | 0.0 | 0.0 |
| 25-34 | 4.4 | 14.2 | 2.7 | 4.2 |
| 35-44 | 21.5 | 63.4 | 6.4 | 15.2 |
| 45+ | 52.4 | 206.7 | 11.4 | 27.9 |
Oral contraceptives may compound the effects of well-known risk factors, such as hypertension, diabetes, hyperlipidemias, age and obesity. In particular, some progestogens are known to decrease HDL cholesterol and cause glucose intolerance, while estrogens may create a state of hyperinsulinism. Oral contraceptives have been shown to increase blood pressure among users (see "WARNINGS"). Similar effects on risk factors have been associated with an increased risk of heart disease. Oral contraceptives must be used with caution in women with cardiovascular disease risk factors.
An increased risk of thromboembolic and thrombotic disease associated with the use of oral contraceptives is well established. Case control studies have found the relative risk of users compared to nonusers 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. Cohort studies have shown the relative risk to be somewhat lower, about 3 for new cases and about 4.5 for new cases requiring hospitalization. The risk of thromboembolic disease due to oral contraceptives is not related to length of use and disappears after pill use is stopped.
A two- to four-fold increase in the relative risk of post-operative thromboembolic complications has been reported with the use of oral contraceptives. The relative risk of venous thrombosis in women who have predisposing conditions is twice that of women without such medical conditions. If feasible, oral contraceptives should be discontinued from at least four weeks prior to and for two weeks after elective surgery of a type associated with an increase in risk of thromboembolism and 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 four to six weeks after delivery.
Oral contraceptives have been shown to increase both the relative and attributable risks of cerebrovascular events (thrombotic and hemorrhagic strokes), although, in general, the risk is greatest among older (>35 years), hypertensive women who also smoke. Hypertension was found to be a risk factor, for both users and nonusers, for both types of strokes, while smoking interacted to increase the risk for hemorrhagic strokes.
In a large study, the relative risk of thrombotic strokes has been shown to range from 3 for normotensive users to 14 for users with severe hypertension. The relative risk of hemorrhagic stroke is reported to be 1.2 for nonsmokers who used oral contraceptives, 2.6 for smokers who did not use oral contraceptives, 7.6 for smokers who used oral contraceptives, 1.8 for normotensive users and 25.7 for users with severe hypertension. The attributable risk is also greater in older women.
A positive association has been observed between the amount of estrogen and progestogen in oral contraceptives and the risk of vascular disease. A decline in serum high-density lipoproteins (HDL) has been reported with many progestational agents. A decline in serum high-density lipoproteins has been associated with an increased incidence of ischemic heart disease. Because estrogens increase HDL cholesterol, the net effect of an oral contraceptive depends on a balance achieved between doses of estrogen and progestogen and the nature and absolute amount of progestogen used in the contraceptive. The amount of both hormones 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 which 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- contraceptive agents should be started on preparations containing the lowest estrogen content which provides satisfactory results in the individual.
There are two studies which have shown persistence of risk of vascular disease for ever-users of oral contraceptives. In a study in the United States, the risk of developing myocardial infarction after discontinuing oral contraceptives persists for at least 9 years for women aged 40 to 49 years who had used oral contraceptives for five or more years, but this increased risk was not demonstrated in other age groups. In another study in Great Britain, the risk of developing cerebrovascular disease persisted for at least 6 years after discontinuation of oral contraceptives, although excess risk was very small. However, both studies were performed with oral contraceptive formulations containing 50 micrograms or higher of estrogens.
One study gathered data from a variety of sources which have estimated the mortality rate associated with different methods of contraception at different ages (Table IV). 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 and older who do not smoke, mortality associated with all methods of birth control is 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. 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 which suggest that the risk of cardiovascular disease with the use of oral contraceptives may now be less than previously observed, 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 which 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, women of all ages who take oral contraceptives, should take the lowest possible dose formulation that is effective.
TABLE IV. 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
| Method of Control and Outcome | 15-19 | 20-24 | 25-29 | 30-34 | 35-39 | 40-44 |
| No fertility control methods\1\ | 7.0 | 7.4 | 9.1 | 14.8 | 25.7 | 28.2 |
| Oral contraceptives | 0.3 | 0.5 | 0.9 | 1.9 | 13.8 | 31.6 |
| non-smoker \2\Oral contraceptives smoker \2\ | 2.2 | 3.4 | 6.6 | 13.5 | 51.1 | 117.2 |
| lUD \2\ | 0.8 | 0.8 | 1.0 | 1.0 | 1.4 | 1.4 |
| Condom \1\ | 1.1 | 1.6 | 0.7 | 0.2 | 0.3 | 0.4 |
| Diaphragm/spermicide \1\ | 1.9 | 1.2 | 1.2 | 1.3 | 2.2 | 2.8 |
| Periodic abstinence \1\ | 2.5 | 1.6 | 1.6 | 1.7 | 2.9 | 3.6 |
| \1\ Deaths are birth related \2\ Deaths are method related Adapted from H.W. Ory, Family Planning Perspectives, 15:57-63, 1983. |
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Numerous epidemiological studies have been performed on the incidence of breast, endometrial, ovarian and cervical cancer in women using oral contraceptives.
The risk of having breast cancer diagnosed may be slightly increased among current and recent users of COCs. However this excess risk appears to decrease over time after COC discontinuation and by 10 years after cessation the increased risk disappears. The risk does not appear to increase with duration of use and no consistent relationships have been found with dose or type of steroid. Most studies show a similar pattern of risk with COC use regardless of a woman's reproductive history or her family breast cancer history. Some studies have found a small increase in risk for women who first use COCs before age 20.
Breast cancers diagnosed in current or previous OC users tend to be less clinically advanced than in nonusers.
Women who currently have or have had breast cancer should not use oral contraceptives because breast cancer is a hormonally-sensitive tumor.
Some studies suggest that oral contraceptive use has been associated with an increase in the risk of cervical intraepithelial neoplasia in some populations of women. 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.
Benign hepatic adenomas are associated with oral-contraceptive use, although the incidence of benign tumors is rare in the United States. Indirect calculations have estimated the attributable risk to be in the range of 3.3 cases/100,000 for users, a risk that increases after four or more years of use. Rupture of rare, benign, hepatic adenomas may cause death through intra-abdominal hemorrhage.
Studies from Britain have shown an increased risk of developing hepatocellular carcinoma in long-term (>8 years) oral contraceptive users. However, these cancers are extremely rare in the U.S. and the attributable risk (the excess incidence) of liver cancers in oral-contraceptive users approaches less than one per million users.
There have been clinical case reports of retinal thrombosis associated with the use of oral contraceptives. Oral contraceptives should be discontinued if there is unexplained partial or complete loss of vision; onset of proptosis or diplopia; papilledema; or retinal vascular lesions. Appropriate diagnostic and therapeutic measures should be undertaken immediately.
Extensive epidemiological studies have revealed no increased risk of birth defects in women who have used oral contraceptives prior to pregnancy. Studies also do not suggest a teratogenic effect, particularly in so far as cardiac anomalies and limb-reduction defects are concerned, when 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. If the patient has not adhered to the prescribed dosing schedule, the possibility of pregnancy should be considered at the time of the first missed period. Oral contraceptive use should be discontinued if pregnancy is confirmed.
Earlier studies have reported an increased lifetime relative risk of gallbladder surgery in users of oral contraceptives and estrogens. More recent studies, however, have shown that the relative risk of developing gallbladder disease among oral-contraceptive users may be minimal. The recent findings of minimal risk may be related to the use of oral-contraceptive formulations containing lower hormonal doses of estrogens and progestogens.
Oral contraceptives have been shown to cause glucose intolerance in a significant percentage of users. Oral contraceptives containing greater than 75 micrograms of estrogens cause hyperinsulinism, while lower doses of estrogen cause less glucose intolerance. Progestogens increase insulin secretion and create insulin resistance, this effect varying with different progestational agents. 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.
A small proportion of women will have persistent hypertriglyceridemia while on the pill. As discussed earlier (see "WARNINGS"), changes in serum triglycerides and lipoprotein levels have been reported in oral-contraceptive users.
An increase in blood pressure has been reported in women taking oral contraceptives and this increase is more likely in older oral contraceptive users and with continued use. Data from the Royal College of General Practitioners 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 disease should be encouraged to use another method of contraception. If women with hypertension 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 and there is no difference in the occurrence of hypertension among ever- and never-users.
The onset or exacerbation of migraine or development of headache with a new pattern which is recurrent, persistent or severe requires discontinuation of oral contraceptives and evaluation of the cause.
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 pathology has been excluded, time or a change to another formulation may solve the problem. In the event of amenorrhea, pregnancy should be ruled out.
Some women may encounter post-pill amenorrhea or oligomenorrhea, especially when such a condition was pre-existent.
Patients should be counseled that this product does not protect against HIV infection (AIDS) and other sexually transmitted diseases.
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.
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.
If jaundice develops in any woman receiving oral contraceptives, the medication should be discontinued. Steroid hormones may be poorly metabolized in patients with impaired liver function.
Oral contraceptives may cause some degree of fluid retention. They should be prescribed with caution, and only with careful monitoring, in patients with conditions which might be aggravated by fluid retention.
Women with a history of depression should be carefully observed and the drug discontinued if depression recurs to a serious degree.
Contact-lens wearers who develop visual changes or changes in lens tolerance should be assessed by an ophthalmologist.
In a 24 month oral carcinogenicity study in mice dosed with 10 mg/kg/day drospirenone alone or 1 + 0.01, 3 + 0.03 and 10 + 0.1 mg/kg/day of drospirenone and ethinyl estradiol, 0.1 to 2 times the exposure (AUC of drospirenone) of women taking a contraceptive dose, there was an increase in carcinomas of the harderian gland in the group that received the high dose of drospirenone alone. In a similar study in rats given 10 mg/kg/day drospirenone alone or 0.3 + 0.003, 3 + 0.03 and 10 + 0.1 mg/kg/day drospirenone and ethinyl estradiol, 0.8 to 10 times the exposure of women taking a contraceptive dose, there was an increased incidence of benign and total (benign and malignant) adrenal gland pheochromocytomas in the group receiving the high dose of drospirenone. Drospirenone was not mutagenic in a number of in vitro (Ames, Chinese Hamster Lung gene mutation and chromosomal damage in human lymphocytes) and in vivo (mouse micronucleus) genotoxicity tests. Drospirenone increased unscheduled DNA synthesis in rat hepatocytes and formed adducts with rodent liver DNA but not with human liver DNA. See WARNINGS
Pregnancy category X. See CONTRAINDICATIONS and WARNINGS Sections. Estrogens and progestins should not be used during pregnancy. Fourteen pregnancies that occurred with YASMIN exposure in utero (none with more than a single cycle of exposure) have been identified. One infant was born with esophageal atresia. A causal association with YASMIN is unknown.
A teratology study in pregnant rats given drospirenone orally at doses of 5, 15 and 45 mg/kg/day, 6 to 50 times the human exposure based on AUC of drospirenone, resulted in an increased number of fetuses with delayed ossification of bones of the feet in the two higher doses. A similar study in rabbits dosed orally with 1, 30 and 100 mg/kg/day drospirenone, 2 to 27 times the human exposure, resulted in an increase in fetal loss and retardation of fetal development (delayed ossification of small bones, multiple fusions of ribs) at the high dose only. When drospirenone was administered with ethinyl estradiol (100:1) during late pregnancy (the period of genital development) at doses of 5, 15 and 45 mg/kg, there was a dose dependent increase in feminization of male rat fetuses. In a study in 36 cynomolgous monkeys, no teratogenic or feminization effects were observed with orally administered drospirenone and ethinyl estradiol (100:1) at doses up to 10 mg/kg/day drospirenone, 30 times the human exposure.
Small amounts of oral-contraceptive steroids have been identified in the milk of nursing mothers, 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.
After oral administration of YASMIN about 0.02% of the drospirenone dose was excreted into the breast milk of postpartum women within 24 hours. This results in a maximal daily dose of about 3 mcg drospirenone in an infant.
Safety and efficacy of YASMIN has been established in women of reproductive age. Safety and efficacy are expected to be the same for postpubertal adolescents under the age of 16 and for users 16 years and older. Use of this product before menarche is not indicated.
See "Patient Labeling" printed below.
Last updated on RxList: 7/10/2007
Serious ill effects have not been reported following acute ingestion of large doses of other oral contraceptives by young children. Overdosage may cause nausea, and withdrawal bleeding may occur in females. Drospirenone, however is a spironolactone analogue which has antimineralcorticoid properties. Serum concentration of potassium and sodium, and evidence of metabolic acidosis, should be monitored in cases of overdose.
The following non-contraceptive health benefits related to the use of oral contraceptives are supported by epidemiological studies which largely utilized oral-contraceptive formulations containing doses exceeding 0.035 mg of ethinyl estradiol or 0.05 mg mestranol.
Effects on menses:
Effects related to inhibition of ovulation:
Effects from long-term use:
YASMIN should not be used in women who have the following:
Last updated on RxList: 7/10/2007
Combination oral contraceptives (COCs) act by suppression of gonadotropins. Although the primary mechanism of this action is inhibition of ovulation, other alterations include changes in the cervical mucus (which increases the difficulty of sperm entry into the uterus) and the endometrium (which reduces the likelihood of implantation).
Drospirenone is a spironolactone analogue with antimineralocorticoid activity. Preclinical studies in animals and in vitro have shown that drospirenone has no androgenic, estrogenic, glucocorticoid, and antiglucocorticoid activity. Preclinical studies in animals have also shown that drospirenone has antiandrogenic activity.
The absolute bioavailability of drospirenone (DRSP) from a single entity tablet is about 76%. The absolute bioavailability of ethinyl estradiol (EE) is approximately 40% as a result of presystemic conjugation and first-pass metabolism. The absolute bioavailability of YASMIN which is a combination tablet of drospirenone and ethinyl estradiol has not been evaluated. Serum concentrations of DRSP and EE reached peak levels within 1-3 hours after administration of YASMIN. After single dose administration of YASMIN, the relative bioavailability, compared to a suspension, was 107% and 117% for DRSP and EE, respectively.
The pharmacokinetics of DRSP are dose proportional following single doses ranging from 1-10 mg. Following daily dosing of YASMIN, steady state DRSP concentrations were observed after 10 days. There was about 2 to 3 fold accumulation in serum Cmax and AUC (0-24h) values of DRSP following multiple dose administration of YASMIN (see Table I).
For EE, steady-state conditions are reported during the second half of a treatment cycle. Following daily administration of YASMIN serum Cmax and AUC (0-24h) values of EE accumulate by a factor of about 1.5 to 2.0.
TABLE OF MEAN PHARMACOKINETIC PARAMETERS OF YASMIN
(Drospirenone 3 mg and Ethinyl Estradiol 0.030 mg )
TABLE I
| Drospirenone Mean (%CV) Values |
|||||
| Cycle / Day | No. of Subjects | Cmax (ng/mL) |
Tmax (h) |
AUC(0-24h) (ng•h/mL) |
t½ (h) |
| 1/1 | 12 | 36.9 (13) | 1.7 (47) | 288 (25) | NA |
| 1/21 | 12 | 87.5 (59) | 1.7 (20) | 827 (23) | 30.9 (44) |
| 6/21 | 12 | 84.2 (19) | 1.8 (19) | 930 (19) | 32.5 (38) |
| 9/21 | 12 | 81.3 (19) | 1.6 (38) | 957 (23) | 31.4 (39) |
| 13/21 | 12 | 78.7 (18) | 1.6 (26) | 968 (24) | 31.1 (36) |
| Ethinyl Estradiol Mean (%CV) Values |
|||||
| Cycle / Day | No. of Subjects | Cmax (pg/mL) |
Tmax (h) |
AUC(0-24h) (pg•h/mL) |
t½ (h) |
| 1/1 | 11 | 53.5 (43) | 1.9 (45) | 280.3 (87) | NA |
| 1/21 | 11 | 92.1 (35) | 1.5 (40) | 461.3 (94) | NA |
| 6/21 | 11 | 99.1 (45) | 1.5 (47) | 346.4 (74) | NA |
| 9/21 | 11 | 87.0 (43) | 1.5 (42) | 485.3 (92) | NA |
| 13/21 | 10 | 90.5 (45) | 1.6 (38) | 469.5 (83) | NA |
| NA = Not available | |||||
The rate of absorption of DRSP and EE following single administration of two YASMIN tablets was slower under fed conditions with the serum Cmax being reduced about 40% for both components. The extent of absorption of DRSP, however, remained unchanged. In contrast the extent of absorption of EE was reduced by about 20% under fed conditions.
DRSP and EE serum levels decline in two phases. The apparent volume of distribution of DRSP is approximately 4 L/kg and that of EE is reported to be approximately 4 - 5 L/kg.
DRSP does not bind to sex hormone binding globulin (SHBG) or corticosteroid binding globulin (CBG) but binds about 97% to other serum proteins. Multiple dosing over 3 cycles resulted in no change in the free fraction (as measured at trough levels). EE is reported to be highly but non-specifically bound to serum albumin (approximately 98.5 %) and induces an increase in the serum concentrations of both SHBG and CBG. EE induced effects on SHBG and CBG were not affected by variation of the DRSP dosage in the range of 2 to 3 mg.
The two main metabolites of DRSP found in human plasma were identified to be the acid form of DRSP generated by opening of the lactone ring and the 4,5-dihydrodrospirenone-3-sulfate. These metabolites were shown not to be pharmacologically active. In in vitro studies with human liver microsomes, DRSP was metabolized only to a minor extent mainly by Cytochrome P450 3A4 (CyP3A4)
EE has been reported to be subject to presystemic conjugation in both small bowel mucosa and the liver. Metabolism occurs primarily by aromatic hydroxylation but a wide variety of hydroxylated and methylated metabolites are formed. These are present as free metabolites and as conjugates with glucuronide and sulfate. CYP3A4 in the liver are responsible for the 2-hydroxylation which is the major oxidative reaction. The 2-hydroxy metabolite is further transformed by methylation and glucuronidation prior to urinary and fecal excretion.
DRSP serum levels are characterized by a terminal disposition phase half-life of approximately 30 hours after both single and multiple dose regimens. Excretion of DRSP was nearly complete after ten days and amounts excreted were slightly higher in feces compared to urine. DRSP was extensively metabolized and only trace amounts of unchanged DRSP were excreted in urine and feces. At least 20 different metabolites were observed in urine and feces. About 38-47% of the metabolites in urine were glucuronide and sulfate conjugates. In feces, about 17-20 % of the metabolites were excreted as glucuronides and sulfates.
For EE the terminal disposition phase half life has been reported to be approximately 24 hours. EE is not excreted unchanged. EE is excreted in the urine and feces as glucuronide and sulfate conjugates and undergoes enterohepatic circulation.
The effect of race on the disposition of YASMIN has not been evaluated.
YASMIN is contraindicated in patients with hepatic dysfunction (also see BOLDED WARNING). The mean exposure to DRSP in women with moderate liver impairment is approximately three times the exposure in women with normal liver function.
YASMIN is contraindicated in patients with renal insufficiency (also see BOLDED WARNING).
The effect of renal insufficiency on the pharmacokinetics of DRSP (3 mg daily for 14 days) and the effect of DRSP on serum potassium levels were investigated in female subjects (n = 28, age 30 - 65) with normal renal function and mild and moderate renal impairment . All subjects were on a low potassium diet. During the study 7 subjects continued the use of potassium sparing drugs for the treatment of the underlying illness. On the 14th day (steady-state) of DRSP treatment, serum DRSP levels in the group with mild renal impairment (creatinine clearance CLcr, 50-80 mL/min) were comparable to those in the group with normal renal function (CLcr, >80 mL/min). The serum DRSP levels were on average 37 % higher in the group with moderate renal impairment (CLcr, 30 - 50 mL/min) compared to those in the group with normal renal function. DRSP treatment was well tolerated by all groups. DRSP treatment did not show any clinically significant effect on serum potassium concentration. Although hyperkalemia was not observed in the study, in five of the seven subjects who continued use of potassium sparing drugs during the study, mean serum potassium levels increased by up to 0.33 mEq/L. Therefore, potential exists for hyperkalemia to occur in subjects with renal impairment whose serum potassium is in the upper reference range, and who are concomitantly using potassium sparing drugs.
Last updated on RxList: 7/10/2007
BRIEF SUMMARY PATIENT PACKAGE INSERT
YASMIN 28 Tablets
(drospirenone and ethinyl estradiol)
containing the following:
21 yellow - "active" tablets
7 white "inert" tablets
This product (like all oral contraceptives) is intended to prevent pregnancy. It does not protect against HIV infection (AIDS) and other sexually transmitted diseases.
YASMIN is different from other birth-control pills because it contains the progestin drospirenone. Drospirenone may increase potassium. Therefore, you should not take YASMIN if you have kidney, liver or adrenal disease because this could cause serious heart and health problems. Other drugs may also increase potassium. If you are currently on daily, long-term treatment for a chronic condition with any of the medications below, you should consult your healthcare provider about whether YASMIN is right for you, and during the first month that you take YASMIN, you should have a blood test to check your potassium level.
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 less than 1% per year when used without missing any pills. The typical failure rate of large numbers of pill users is less than 5% per year when women who miss pills are included. However, forgetting to take pills considerably increases the chances of pregnancy.
For the majority of women, oral contraceptives can be taken safely. But there are some women who are at high risk of developing certain serious diseases that can be life-threatening or may cause temporary or permanent disability or death. The risks associated with taking oral contraceptives increase significantly if you:
You should not take the pill if you suspect you are pregnant or have unexplained vaginal bleeding.
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 should not smoke.
Most side effects of the pill are not serious. The most common such effects are nausea, vomiting, bleeding between menstrual periods, weight gain, breast tenderness, and difficulty wearing contact lenses. These side effects, especially nausea and vomiting may subside within the first three months of use.
The serious side effects of the pill occur very infrequently, especially if you are in good health and are young. However, you should know that the following medical conditions have been associated with or made worse by the pill:
Taking the pill provides some important non-contraceptive benefits. These include less painful menstruation, less menstrual blood loss and anemia, fewer pelvic infections, and fewer cancers of the ovary and the lining of the uterus.
Be sure to discuss any medical condition you may have with your healthcare provider. Your healthcare provider will take a medical and family history before prescribing oral contraceptives and will examine you. The physical examination may be delayed to another time if you request it and the healthcare provider believes that it is appropriate to postpone it. You should be reexamined at least once a year while taking oral contraceptives. The detailed patient information booklet gives you further information which you should read and discuss with your healthcare provider.
This product (like all oral contraceptives) is intended to prevent pregnancy. It does not protect against HIV infection (AIDS) and other sexually transmitted diseases such as chlamydia, genital herpes, genital warts, gonorrhea, hepatitis B, and syphilis.
INSTRUCTIONS TO PATIENTS
HOW TO TAKE THE PILL
IMPORTANT POINTS TO REMEMBER
BEFORE YOU START TAKING YOUR PILLS:
1. DECIDE WHAT TIME OF DAY YOU WANT TO TAKE YOUR PILL. It is important to take it at about the same time every day.
2. LOOK AT YOUR PILL PACK- IT HAS 28 PILLS:
The YASMIN-pill pack has 21 yellow "active" pills (with hormones) to be taken for three weeks, followed by 7 white "reminder" pills (without hormones) to be taken for one week.
3. ALSO FIND:
START
| Monday | Tuesday | Wednesday | Thursday | Friday | Saturday | Sunday | |
| >Week 1 | O | O | O | O | O | O | O |
| >Week 2 | O | O | O | O | O | O | O |
| >Week 3 | O | O | O | O | O | O | O |
| >Week 4 | O | O | O | O | O | O | O |
YASMIN 28 Tablets
(drospirenone and ethinyl estradiol)
4. BE SURE YOU HAVE READY AT ALL TIMES:
ANOTHER KIND OF BIRTH CONTROL (such as condoms or spermicides) to use as a back-up in case you miss pills.
AN EXTRA, FULL PILL PACK.
You have a choice for which day to start taking your first pack of pills. Decide with your doctor or clinic which is the best day for you. Pick a time of day which will be easy to remember.
1. TAKE ONE PILL AT THE SAME TIME EVERY DAY UNTIL THE PACK IS EMPTY
Do not skip pills even if you are spotting or bleeding between monthly periods or feel sick to your stomach (nausea).
Do not skip pills even if you do not have sex very often.
2. WHEN YOU FINISH A PACK OR SWITCH YOUR BRAND OF PILLS:
Start the next pack on the day after your last white "reminder" pill. Do not wait any days between packs.
If you MISS 1 yellow "active" pill:
If you MISS 2 yellow "active" pills in a row in WEEK 1 OR WEEK 2 of your pack:
If you MISS 2 yellow "active" pills in a row in THE 3rd WEEK:
If you MISS 3 OR MORE yellow "active" pills in a row (during the first 3 weeks).
If you forget any of the 7 white "reminder" pills in Week 4:
THROW AWAY the pills you missed.
Keep taking one pill each day until the pack is empty.
You do not need a back-up method.
FINALLY, IF YOU ARE STILL NOT SURE WHAT TO DO ABOUT THE PILLS YOU HAVE MISSED:
Use a BACK-UP METHOD (such as condoms or spermicides) anytime you have sex.
KEEP TAKING ONE ACTIVE PILL EACH DAY until you can reach your doctor or clinic.
For additional information see "Detailed Patient Labeling"
This product (like all oral contraceptives) is intended to prevent pregnancy. It does not protect against HIV infection (AIDS) and other sexually transmitted diseases
YASMIN is different from other birth-control pills because it contains the progestin drospirenone. Drospirenone may increase potassium. Therefore, you should not take YASMIN if you have kidney, liver or adrenal disease because this could cause serious heart and health problems. Other drugs may also increase potassium. If you are currently on daily, long-term treatment for a chronic condition with any of the medications below, you should consult your healthcare provider about whether YASMIN is right for you, and during the first month that you take YASMIN, you should have a blood test to check your potassium level.
Any woman who considers using oral contraceptives (the birth-control pill or the "pill") should understand the benefits and risks of using this form of birth control. This leaflet will give you much of the information you will need to make this decision and will also help you determine if you are at risk of developing any of the serious side effects of the pill. It will tell you how to use the pill properly so that it will be as effective as possible. However, this leaflet is not a replacement for a careful discussion between you and your healthcare 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 healthcare provider's advice with regard to regular check-up while you are on the pill.
Oral contraceptives or "birth-control pills" or "the pill" are used to prevent pregnancy and are more effective than other nonsurgical methods of birth control. When they are taken correctly, the chance of becoming pregnant is less than 1.0% (one pregnancy per 100 women per year of use) when used perfectly, without missing any pills. Typical failure rates, including women who don't always follow the instructions exactly, are about 5.0% per year. The chance of becoming pregnant increases with each missed pill during a menstrual cycle.
In comparison, typical failure rates for other nonsurgical methods of birth control during the first year of use are as follows:
Percentage of women experiencing a unintended pregnancy during the first year of typical use and first year of perfect use of contraception and the percentage continuing use at the end of the first year: United States.
| Use | % of Women Experiencing an Accidental Pregnancy with in the First Year of Use |
% of Women Continuing |
|
| Method (1) |
Typical Use1 (2) |
Perfect Use2 (3) |
(4) |
| Chance4 | 85 | 85 | |
| Spermicides5 | 26 | 6 | 40 |
| Periodic abstinence | 25 | 63 | |
| Calendar | 9 | ||
| Ovulation method | 3 | ||
| Sympto-thermal6 | 2 | ||
| Post-ovulation | 1 | ||
| Withdrawal | 19 | 4 | |
| Cap7 | |||
| Parous women | 40 | 26 | 42 |
| Nulliparous women | 20 | 9 | 56 |
| Sponge | |||
| Parous women | 40 | 20 | 42 |
| Nulliparous women | 20 | 9 | 56 |
| Diaphragm7 | 20 | 6 | 56 |
| Condom8 | |||
| Female (Reality) | 21 | 5 | 56 |
| Male | 14 | 3 | 61 |
| Pill | 5 | 71 | |
| progestin only | 0.5 | ||
| combined | 0.1 | ||
| IUD: | |||
| Progesterone T: | 2.0 | 1.5 | 81 |
| Copper T 380A | 0.8 | 0.6 | 78 |
| Lng 20 | 0.1 | 0.1 | 81 |
| Depo Provera | 0.3 | 0.3 | 70 |
| Norplant and Norplant-2 | 0.05 | 0.05 | 88 |
| Female sterilization | 0.5 | 0.5 | 100 |
| Male sterilization | 0.15 | 0.10 | 100 |
| Emergency Contraceptive Pills: Treatment
initiated within 72 hours after unprotected intercourse reduces the risk
of pregnancy by at least 75%.9 Lactational Amenorrhea Method: LAM is highly effective, temporary method of contraception. 10Source: Trussell J, Contraceptive efficacy. In Hatcher RA, Trussell J, Stewart F, Cates W, Stewart GK, Kowal D, Guest F, Contraceptive Technology: Seventeenth Revised Edition. New York NY: Irvington Publishers, 1998. 1 Among typical couples who initiate use of a method (not necessarily for the first time), the percentage who experience an accidental pregnancy during the first year if they do not stop use for any other reason. 2 Among couples who initiate use of a method (not necessarily for the first time) and who use it perfectly (both consistently and correctly). the percentage who experience an accidental pregnancy during the first year if they do not stop use for any reason. 3 Among couples attempting to avoid pregnancy, the percentage who continue to use a method for one year. 4 The percents becoming pregnant in columns (2) and (3) are based on data from populations where contraception is not used and from women who cease using contraception in order to become pregnant. Among such populations, about 89% become pregnant within one year. This estimate was lowered slightly (to 85%) to represent the percentage who would become pregnant within one year among women now relying on reversible methods of contraception if they abandoned contraception altogether. 5 Foams, creams, gels vaginal suppositories, and vaginal film. 6 Cervical mucus (ovulation) method supplemented by calendar in the pre-ovulatory and basal body temperature in the post-ovulatory phases. 7 With spermicidal cream or jelly 8 Without spermicides. 9 The treatment schedule is one dose within 72 hours after unprotected intercourse, and a second dose 12 hours after the first dose. The Food and Drug Administration has declared the following brands of oral contraceptives to be safe and effective for emergency contraception: Ovral (1 dose is 2 white pills), Alesse (1 dose is 5 pink pills), Nordette or Levlen (1 dose is 2 light-orange pills), Lo/Ovral (1 dose is 4 white pills), Triphasil or Tri-Levlen (1 dose is 4 yellow pills). 10 However, to maintain effective protection against pregnancy, another method of contraception must be used as soon as menstruation resumes, the frequency or duration of breastfeeds is reduced, bottle feeds are introduced, or the baby reaches six months of age. |
|||
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 should not smoke.
Some women should not use the pill YASMIN. For example, you should not take the pill YASMIN if you are pregnant or think you may be pregnant. You should also not use the pill YASMIN if you have had any of the following conditions:
In addition, you should not use YASMIN if you have any of the following conditions:
Tell your healthcare provider if you have ever had any of the above conditions (Your healthcare provider can recommend another method of birth control). If you are currently on daily, long-term treatment for a chronic condition with any of the following medications, you should consult your healthcare provider before taking YASMIN:
OTHER CONSIDERATIONS BEFORE TAKING ORAL CONTRACEPTIVES Tell your healthcare provider if you or any family member has ever had:
Women with any of these conditions should be checked often by their healthcare provider if they choose to use oral contraceptives.
Also, be sure to inform your doctor or healthcare provider if you smoke or are on any medications.
All methods of birth control and pregnancy are associated with a risk of developing certain diseases which may lead to disability or death. An estimate of the number of deaths associated with different methods of birth control and pregnancy has been calculated and is shown in the following table.
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
| Method of Control and Outcome | 15-19 | 20-24 | 25-29 | 30-34 | 35-39 | 40-44 |
| No fertility control methods\1\ | 7.0 | 7.4 | 9.1 | 14.8 | 25.7 | 28.2 |
| Oral contraceptives non-smoker \2\ | 0.3 | 0.5 | 0.9 | 1.9 | 13.8 | 31.6 |
| Oral contraceptives smoker \2\ | 2.2 | 3.4 | 6.6 | 13.5 | 51.1 | 117.2 |
| lUD \2\ | 0.8 | 0.8 | 1.0 | 1.0 | 1.4 | 1.4 |
| Condom \1\ | 1.1 | 1.6 | 0.7 | 0.2 | 0.3 | 0.4 |
| Diaphragm/spermicide \1\ | 1.9 | 1.2 | 1.2 | 1.3 | 2.2 | 2.8 |
| Periodic abstinence \1\ | 2.5 | 1.6 | 1.6 | 1.7 | 2.9 | 3.6 |
| \1\ Deaths are birth related \2\ Deaths are method related Adapted from H.W. Ory, Family Planning Perspectives, 15:57-63, 1983. |
||||||
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- 25.7 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, except for those women over the age of 40, when the risk increases to 31.6 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 women) in that age group.
The suggestion that women over 40 who do not smoke should not take oral contraceptives is based on information from older high-dose pills and on less-selective use of pills than is practiced today. An Advisory Committee of the FDA discussed this issue in 1989 and recommended that the benefits of oral contraceptive use by healthy, non-smoking women over 40 years of age may outweigh the possible risks. However, all women, especially older women, are cautioned to use the lowest-dose pill that is effective.
If any of these adverse effects occur while you are taking oral contraceptives, call your doctor immediately:
If any of these side effects bother you, call your doctor or healthcare provider.
IMPORTANT POINTS TO REMEMBER
BEFORE YOU START TAKING YOUR PILLS:
BEFORE YOU START TAKING YOUR PILLS
1. DECIDE WHAT TIME OF DAY YOU WANT TO TAKE
YOUR PILL.
It is important to take it at about the same time every day.
2. LOOK AT YOUR PILL PACK -IT HAS 28 PILLS
The YASMIN-pill pack has 21 yellow "active" pills (with hormones)
to be taken for three weeks, followed by 7 white "reminder" pills
(without hormones) to be taken for one week.
3. ALSO FIND:
START
| Monday | Tuesday | Wednesday | Thursday | Friday | Saturday | Sunday | |
| >Week 1 | O | O | O | O | O | O | O |
| >Week 2 | O | O | O | O | O | O | O |
| >Week 3 | O | O | O | O | O | O | O |
| >Week 4 | O | O | O | O | O | O | O |
YASMIN 28 Tablets
(drospirenone and ethinyl estradiol)
4. BE SURE YOU HAVE READY AT ALL TIMES:
ANOTHER KIND OF BIRTH CONTROL (such as condoms or spermicides) to use as a back-up
in case you miss pills.
AN EXTRA, FULL PILL PACK.
WHEN TO START THE FIRST PACK OF PILLS
You have a choice for which day to start taking your first pack of pills. Decide with your doctor or clinic which is the best day for you. Pick a time of day which will be easy to remember.
DAY 1 START:
SUNDAY START:
WHAT TO DO DURING THE MONTH
WHAT TO DO IF YOU MISS PILLS
If you MISS 1 yellow "active" pill:
If you MISS 2 yellow "active" pills in a row in WEEK 1 OR WEEK 2 of your pack:
If you MISS 2 yellow "active" pills in a row in THE 3rd WEEK:
If you MISS 3 OR MORE yellow "active" pills in a row (during the first 3 weeks).
If you forget any of the 7 white "reminder" pills in Week 4: THROW AWAY the pills you missed. Keep taking one pill each day until the pack is empty. You do not need a back-up method.
FINALLY, IF YOU ARE STILL NOT SURE WHAT TO DO ABOUT THE PILLS YOU HAVE MISSED:
Use a BACK-UP METHOD (such as condoms or spermicides) anytime you have sex.
KEEP TAKING ONE ACTIVE PILL EACH DAY until you can reach your doctor or clinic.
The incidence of pill failure resulting in pregnancy is approximately less than 1.0% (one pregnancy per 100 women per year or use) if taken every day as directed, but more typical failure rates are about 5.0 %. If failure does occur with YASMIN use, the risk to the fetus is unknown.
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 soon after stopping the pill.
Serious ill effects have not been reported following ingestion of large doses of other oral contraceptives by young children. Overdosage of YASMIN may cause nausea and withdrawal bleeding in females and may increase blood levels of potassium or decrease blood levels of sodium, which could be dangerous. In case of overdosage, contact your healthcare provider.
Your healthcare provider will take a medical and family history before prescribing oral contraceptives and will examine you. The physical examination may be delayed to another time if you request it and the healthcare provider believes that it is appropriate to postpone it. You should be re-examined at least once a year. Be sure to inform your healthcare provider if there is a family history of any of the conditions listed previously in this leaflet. Be sure to keep all appointments with your healthcare 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.
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 Prescribing Information which you may wish to read.
Last updated on RxList: 7/10/2007
IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.
ETHINYL ESTRADIOL/DROSPIRENONE - ORAL
(ETH-in-il ess-tra-DYE-ole/droh-SPYE-re-none)
COMMON BRAND NAME(S): Yasmin 28
WARNING: Smoking cigarettes/using tobacco while using hormonal birth control (pill/patch/ring) increases your risk of heart problems and stroke. Do not smoke. The risk of heart problems increases with age (especially in women over 35) and with frequent smoking (15 or more cigarettes a day).
USES: This medication is used to prevent pregnancy. It contains 2 hormones (drospirenone, a progestin, and ethinyl estradiol, an estrogen). These hormones prevent pregnancy by preventing the release of an egg (ovulation). They also change the womb and cervical mucus, making it more difficult for an egg to meet sperm (fertilization) or for the fertilized egg to attach to the wall of the womb (implantation).
Besides preventing pregnancy, birth control pills have been shown to help make your periods more regular, decrease blood loss and painful periods (dysmenorrhea), and decrease your risk of ovarian cysts.
Use of this medication does not protect you or your partner against sexually transmitted diseases (e.g., HIV, gonorrhea, chlamydia).
HOW TO USE: Read the Patient Information Leaflet provided by your pharmacist before you start using this product and each time you get a refill. The leaflet contains very important information on when to take your pills and what to do if you miss a dose. If you have any questions, consult your doctor or pharmacist.
Take this medication by mouth once daily or as directed by your doctor. Pick a time of day that is easy for you to remember, and take your pill at the same time each day.
It is very important to continue taking this medication exactly as prescribed by your doctor. Follow the package instructions to find the first tablet, start with the first tablet in the pack, and take them in the correct order. Do not skip any doses. Pregnancy is more likely if you miss pills, start a new pack late, or take your pill at a different time of the day than usual.
Taking this medication after your evening meal or at bedtime may help if you have stomach upset or nausea with the medication. You may choose to take this medication at another time of day that is easier for you to remember. No matter what dosing schedule you use, it is very important that you take this medication at the same time each day, 24 hours apart. Ask your doctor or pharmacist if you have any questions.
Your pill pack contains 21 pills with active medication. It may also contain 7 reminder pills with no medication. Take one active pill (with hormones) once daily for 21 days in a row. If you are using a product with 28 tablets, take an inactive pill once daily for 7 days in a row after you have taken the last active pill unless otherwise directed by your doctor. If you are using a product with 21 tablets, do not take any tablets for 7 days unless otherwise directed by your doctor. You should have your period during the fourth week of the cycle. After you have taken the last inactive tablet in the pack or gone 7 days without taking an active tablet, start a new pack the next day whether or not you have your period. If you do not get your period, consult your doctor.
If this is the first time you are using this medication and you are not switching from another form of hormonal birth control (e.g., patch, other birth control pills), take the first tablet in the pack on the first Sunday following the beginning of your menstrual period or on the first day of your period. If your period begins on a Sunday, begin taking this medication on that day. For the first cycle of use only, use an additional form of non-hormonal birth control (e.g., condoms, spermicide) for the first 7 days to prevent pregnancy until the medication has enough time to work. If you start on the first day of your period, you do not need to use back-up birth control the first week.
Ask your doctor or pharmacist for information about how to switch from other forms of hormonal birth control (e.g., patch, other birth control pills) to this product. If any of this information is unclear, consult the Patient Information Leaflet or your doctor or pharmacist.
Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.
Tell your doctor immediately if any of these serious side effects occur: changes in vaginal bleeding (e.g., continuous spotting, sudden heavy bleeding, missed periods), problem wearing contact lenses, dark patches on the skin (melasma), unwanted facial/body hair, swelling of the ankles/feet, weight changes (gain or loss).
This medication may rarely cause serious (sometimes fatal) problems from blood clots (e.g., pulmonary embolism, stroke, heart attack). Seek immediate medical attention if you experience: sudden shortness of breath, chest/jaw/left arm pain, confusion, coughing up blood, sudden dizziness/fainting, pain/swelling/warmth in the groin/calf, tingling/weakness/numbness in the arms/legs, headaches that are different from those you may have experienced in the past (e.g., headaches with other symptoms such as vision changes/lack of coordination, existing migraines becoming worse, sudden/very severe headaches), slurred speech, weakness on one side of the body, vision problems/changes.
Tell your doctor immediately if any of these rare but very serious side effects occur: lumps in the breast, severe stomach/abdominal/pelvic pain, mental/mood changes (e.g., depression, suicidal thoughts, persistent trouble sleeping), unusual tiredness, dark urine, yellowing eyes/skin.
A very serious allergic reaction to this drug is unlikely, but seek immediate medical attention if it occurs. Symptoms of a serious allergic reaction include: rash, itching, swelling, severe dizziness, trouble breathing.
This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.
Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.
PRECAUTIONS: See also Warning section.
Before using this medication, tell your doctor or pharmacist if you are allergic to ethinyl estradiol, drospirenone, or spironolactone; or to other estrogens or progestins; or if you have any other allergies.
This medication should not be used if you have certain medical conditions. Before using this product, consult your doctor or pharmacist if you have: adrenal gland problems, history of stroke or other blood clots (e.g., in the legs, eyes, lungs), severe high blood pressure, abnormal breast exam, cancer (especially endometrial or breast cancer), diabetes that has caused kidney/eye/nerve/blood vessel disease, severe headaches, history of heart disease (e.g., heart attack, chest pain), heart valve disease, kidney problems, liver problems (e.g., liver tumor, active liver disease), current or suspected pregnancy, recent major surgery, long periods of sitting or lying down (e.g., immobility such as being bedridden), history of yellowing eyes/skin (jaundice) during pregnancy or while using birth control pills, unexplained vaginal bleeding, heavy tobacco use (especially if 35 or over).
Before using this product, tell your doctor your medical history, especially of: high blood pressure, high cholesterol or triglyceride (blood fat) levels, depression, diabetes, swelling (edema), gallbladder problems, migraine, obesity, irregular/missed/very light periods, recent pregnancy, thyroid problems.
Do not smoke cigarettes or use tobacco. Hormonal birth control (e.g., pills, injections, devices) combined with smoking significantly increases your risk for stroke, blood clots, high blood pressure, and heart attacks, especially in women older than 35. For more details, ask your doctor or pharmacist, or consult the Patient Information Leaflet that comes with this product.
If you have diabetes, this medication may make it harder to control your blood sugar levels. Monitor your blood sugar regularly as directed by your doctor. Tell your doctor the results and any symptoms such as increased thirst/urination. Your anti-diabetic medication or diet may need to be adjusted.
Notify your doctor beforehand if you will be having surgery or will be confined to a chair/bed for a long time (e.g., a long plane flight). You may need to stop the medication for a time or take special precautions.
This medication may cause blotchy, dark areas on your skin (melasma). Sunlight may worsen this effect. Avoid prolonged sun exposure, sunlamps, and tanning booths. Use a sunscreen, and wear protective clothing when outdoors.
If you are nearsighted or wear contact lenses, you may develop vision problems or trouble wearing your contact lenses. Contact your eye doctor if these problems occur.
It may take longer for you to become pregnant after you stop taking birth control pills. Consult your doctor.
This medication must not be used during pregnancy. If you become pregnant or think you may be pregnant, tell your doctor immediately. If you have just given birth or had a pregnancy loss/abortion after the first 3 months, talk with your doctor about reliable forms of birth control, and find out when it is safe to start using birth control that contains a form of estrogen, such as this medication.
This medication passes into breast milk. This may affect milk production and may have harmful effects on a nursing infant. Breast-feeding is not recommended while using this product. Consult your doctor before breast-feeding.
This drug should not be used with the following medications because very serious interactions may occur: aromatase inhibitors (e.g., anastrazole, exemestane), sodium tetradecyl sulfate, troleandomycin.
If you are currently using any of these medications listed above, tell your doctor or pharmacist before starting this medication.
Before taking this medication, tell your doctor of all prescription and nonprescription medications you may use, especially of: medications that can raise potassium levels (e.g., ACE inhibitors such as enalapril/lisinopril, angiotensin receptor blockers such as losartan/valsartan, heparin, NSAIDs such as ibuprofen/naproxen, potassium-sparing "water pills"/diuretics such as spironolactone/triamterene), potassium supplement/salt substitutes, raloxifene, tamoxifen, medication for underactive thyroid (hypothyroidism), drugs that may increase blood levels of this drug (e.g., acetaminophen, ascorbic acid/vitamin C, atorvastatin, azole antifungals such as itraconazole/ketoconazole/vaginal miconazole).
Certain drugs can decrease the effectiveness of combination-type birth control by decreasing the amount of birth control hormones in your system. This can result in pregnancy. These drugs include: many antibiotics (e.g., cephalosporins, chloramphenicol, macrolides such as erythromycin, penicillins, sulfas), aprepitant, bexarotene, bosentan, dapsone, felbamate, griseofulvin, certain HIV protease inhibitors (e.g., amprenavir, nelfinavir, ritonavir), modafinil, nevirapine, phenylbutazone, rifamycins (e.g., rifampin), many seizure medications (e.g., barbiturates, carbamazepine, phenytoin, lamotrigine, topiramate), St. John's wort. Consult your doctor or pharmacist for details, and ask if you should use additional reliable birth control methods while taking any of the drugs listed above.
This drug can speed up or slow down the removal of other drugs from your body by affecting certain liver enzymes. These affected drugs include acetaminophen, aspirin, certain beta blockers (e.g., metoprolol), clofibrate, cyclosporine, morphine, corticosteroids such as prednisolone, certain benzodiazepines such as lorazepam/temazepam, and theophylline, among others. If you are currently using any of these medications listed above, tell your doctor or pharmacist before starting this medication.
This medication can affect the results of certain lab tests (e.g., blood tests for clotting factors, thyroid). Make sure laboratory personnel and all your doctors know you use this medication.
This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.
OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US national poison hotline at 1-800-222-1222. Canadian residents should call their local poison control center directly. Symptoms of overdose may include severe nausea and vomiting. Females may experience sudden/unusual vaginal bleeding.
NOTES: Do not share this medication with others.
Keep all appointments with your doctor and the laboratory. Laboratory tests (e.g., potassium levels) may be performed to monitor for possible side effects to this medication. You should have regular complete physical exams including blood pressure, breast exam, pelvic exam, and screening for cervical cancer (pap smear). Follow your doctor's instructions for examining your own breasts, and report any lumps immediately. Consult your doctor for more details.
MISSED DOSE: Read the package information for advice on missed doses. You may need to use back-up birth control (e.g., condoms, spermicide) to prevent pregnancy. Ask your doctor or pharmacist if you have any questions.
If you often forget to take your pills as directed, contact your doctor to discuss switching to another form of birth control.
STORAGE: Store at room temperature at 77 degrees F (25 degrees C). Brief storage between 59-86 degrees F (15-30 degrees C) is permitted. Do not store in the bathroom. Keep all medicines away from children and pets.
Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.
Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.
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