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MIRCETTE

 * Generic Name: desogestrel, ethinyl estradiol and ethinyl estradiol
 * Brand Name: Mircette
 * Drug Class: Contraceptives, Oral, Estrogens/Progestins

Medical Editor: John P. Cunha, DO, FACOEP Last updated on RxList: 1/12/2023

home drugs a-z list mircette (desogestrel, ethinyl estradiol and ethinyl
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DRUG SUMMARY

WHAT IS MIRCETTE?

Mircette (desogestrel/ethinyl estradiol and ethinyl estradiol) is a combination
of female hormones indicated for the prevention of pregnancy in women. Mircette
is available in generic form.

WHAT ARE SIDE EFFECTS OF MIRCETTE?

Mircette may cause serious side effects including:

 * hives,
 * difficulty breathing,
 * swelling of your face, lips, tongue, or throat,
 * sudden numbness or weakness (especially on one side of the body),
 * sudden sever headache,
 * slurred speech,
 * problems with vision or balance,
 * sudden vision loss,
 * stabbing chest pain,
 * shortness of breath,
 * coughing up blood,
 * pain or warmth in one or both legs,
 * chest pain or pressure,
 * pain spreading to your jaw or shoulder,
 * nausea,
 * sweating,
 * loss of appetite,
 * upper stomach pain,
 * tiredness,
 * fever,
 * dark urine,
 * clay-colored stools,
 * yellowing of the skin or eyes (jaundice),
 * severe headache,
 * blurred vision,
 * pounding in your neck or ears,
 * swelling in your hands, ankles, or feet,
 * changes in the pattern or severity of migraine headaches,
 * breast lump,
 * sleep problems,
 * weakness,
 * tired feeling, and
 * mood changes

Get medical help right away, if you have any of the symptoms listed above.

Common side effects of Mircette include:

 * nausea (especially when you first start taking Mircette),
 * vomiting,
 * bloating,
 * stomach cramps,
 * breast tenderness or swelling,
 * nipple discharge,
 * freckles or darkening of facial skin,
 * increased hair growth,
 * loss of scalp hair,
 * changes in weight or appetite,
 * problems with contact lenses,
 * vaginal itching or discharge,
 * changes in your menstrual periods, or
 * decreased sex drive.

Cigarette smoking increases the risk of serious cardiovascular side effects.
Tell your doctor if you have serious side effects of Mircette including:

 * lumps in the breast,
 * mental/mood changes (such as new or worsening depression),
 * severe stomach or abdominal pain,
 * unusual changes in vaginal bleeding (such as continuous spotting, sudden
   heavy bleeding, missed periods),
 * dark urine, or
 * yellowing eyes or skin.

Seek medical care or call 911 at once if you have the following serious side
effects:

 * Serious eye symptoms such as sudden vision loss, blurred vision, tunnel
   vision, eye pain or swelling, or seeing halos around lights;
 * Serious heart symptoms such as fast, irregular, or pounding heartbeats;
   fluttering in your chest; shortness of breath; and sudden dizziness,
   lightheartedness, or passing out;
 * Severe headache, confusion, slurred speech, arm or leg weakness, trouble
   walking, loss of coordination, feeling unsteady, very stiff muscles, high
   fever, profuse sweating, or tremors.

This document does not contain all possible side effects and others may occur.
Check with your physician for additional information about side effects.

DOSAGE FOR MIRCETTE

Mircette tablets must be taken exactly as directed and at intervals not
exceeding 24 hours.

WHAT DRUGS, SUBSTANCES, OR SUPPLEMENTS INTERACT WITH MIRCETTE?

Mircette may interact with rifampin, barbiturates, phenylbutazone, phenytoin
sodium, carbamazepine, griseofulvin, ampicillin, tetracyclines, bosentan, drugs
to treat hepatitis C or HIV/AIDS, St. John's wort, seizure medications,
dantrolene, lamotrigine, tizanidine, or tranexamic acid. Tell your doctor all
medications and supplements you use.

MIRCETTE DURING PREGNANCY OR BREASTFEEDING

Mircette is not recommended for use during pregnancy. Tell your doctor right
away if you become pregnant while taking Mircette. Hormones in Mircette pass
into breast milk and may harm a nursing baby. Mircette may also slow milk
production. Mircette is not recommended for use while breastfeeding.

ADDITIONAL INFORMATION

Our Mircette (desogestrel/ethinyl estradiol and ethinyl estradiol) Side Effects
Drug Center provides a comprehensive view of available drug information on the
potential side effects when taking this medication.


FDA DRUG INFORMATION

 * Drug Description
 * Indications
 * Dosage
 * Side Effects
 * Drug Interactions
 * Warnings
 * Precautions
 * Overdose
 * Contraindications
 * Clinical Pharmacology
 * Medication Guide

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


DESCRIPTION FOR MIRCETTE

Mircette® (desogestrel/ethinyl estradiol and ethinyl estradiol) Tablets provide
an oral contraceptive regimen of 21 white round tablets each containing 0.15 mg
desogestrel (13-ethyl11- methylene-18,19-dinor-17 alpha-pregn- 4-en-
20-yn-17-ol), 0.02 mg ethinyl estradiol (19-nor17 alpha-pregna-1,3,5
(10)-trien-20-yne-3,17-diol), and inactive ingredients which include colloidal
silicon dioxide, hypromellose, lactose monohydrate, polyethylene glycol,
povidone, pregelatinized starch, stearic acid and vitamin E, followed by 2 inert
light-green round tablets with the following inactive ingredients: FD&C blue no.
1 aluminum lake, FD &C yellow no. 6 aluminum lake, D&C yellow no. 10 aluminum
lake, lactose monohydrate, magnesium stearate, microcrystalline cellulose and
pregelatinized starch. Mircette® also contains 5 yellow round tablets containing
0.01 mg ethinyl estradiol (19-nor-17 alpha-pregna-1,3,5
(10)-trien-20-yne3,17-diol) and inactive ingredients which include colloidal
silicon dioxide, D&C yellow no. 10, aluminum lake, FD&C yellow no. 6 aluminum
lake, hypromellose, lactose monohydrate, polyethylene glycol, povidone,
polysorbate 80, pregelatinized starch, stearic acid, titanium dioxide and
vitamin E. The molecular weights for desogestrel and ethinyl estradiol are
310.48 and 296.40 respectively. The structural formulas are as follows:










USES FOR MIRCETTE

Mircette is indicated for the prevention of pregnancy in women who elect to use
this product as a method of contraception. 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 these
methods can result in lower failure rates.

TABLE II: Percentage of women experiencing an unintended pregnancy during the
first year of typical use and the first year of perfect use of contraception and
the percentage continuing use at the end of the first year, United States.

Method (1) % of Women Experiencing an Unintended Pregnancy within the First Year
of Use % of Women Continuing Use at One Yeara (4) Typical Useb (2) Perfect Usec
(3) Chanced 85 85 Spermicidese 26 6 40 Periodic abstinence 25 63 Calendar 9
Ovulation Method 3 Sympto-Thermalf 2 Post-Ovulation 1 Withdrawal 19 4 Capg
Parous Women 40 26 42 Nulliparous Women 20 9 56 Sponge Parous Women 40 20 42
Nulliparous Women 20 9 56 Diaphragmg 20 6 56 Condomh 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 a) Among couples attempting to avoid pregnancy, the
percentage who continue to use a method for one year.
b) 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.
c) 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 other reason.
d) 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 percent who would become pregnant within one year among women now
relying on reversible methods of contraception if they abandoned contraception
altogether.
e) Foams, creams, gels, vaginal suppositories, and vaginal film.
f) Cervical mucus (ovulation) method supplemented by calendar in the
pre-ovulatory and basal body temperature in the post-ovulatory phases.
g) With spermicidal cream or jelly.
h) Without spermicides.




DOSAGE FOR MIRCETTE

To achieve maximum contraceptive effectiveness, Mircette must be taken exactly
as directed and at intervals not exceeding 24 hours. Mircette may be initiated
using either a Sunday start or a Day 1 start.

NOTE: Each cycle pack dispenser is preprinted with the days of the week,
starting with Sunday, to facilitate a Sunday start regimen. Six different “day
label strips” are provided with each cycle pack dispenser in order to
accommodate a Day 1 start regimen. In this case, the patient should place the
self-adhesive “day label strip” that corresponds to her starting day over the
preprinted days.

IMPORTANT: The possibility of ovulation and conception prior to initiation of
use of Mircette should be considered.

The use of Mircette for contraception may be initiated 4 weeks postpartum in
women who elect not to breast-feed. When the tablets are administered during the
postpartum period, the increased risk of thromboembolic disease associated with
the postpartum period must be considered (see CONTRAINDICATIONS and WARNINGS
concerning thromboembolic disease. See also PRECAUTIONS for Nursing mothers).

If the patient starts on Mircette postpartum, and has not yet had a period, she
should be instructed to use another method of contraception until a white tablet
has been taken daily for 7 days.

SUNDAY START

When initiating a Sunday start regimen, another method of contraception should
be used until after the first 7 consecutive days of administration.

Using a Sunday start, tablets are taken daily without interruption as follows:
The first white tablet should be taken on the first Sunday after menstruation
begins (if menstruation begins on Sunday, the first white tablet is taken on
that day). One white tablet is taken daily for 21 days, followed by 1
light-green (inert) tablet daily for 2 days and 1 yellow (active) tablet daily
for 5 days. For all subsequent cycles, the patient then begins a new 28-tablet
regimen on the next day (Sunday) after taking the last yellow tablet. [If
switching from a Sunday start oral contraceptive, the first Mircette
(desogestrel/ethinyl estradiol and ethinyl estradiol) Tablet should be taken on
the second Sunday after the last tablet of a 21 day regimen or should be taken
on the first Sunday after the last inactive tablet of a 28 day regimen.]

If a patient misses 1 white tablet, she should take the missed tablet as soon as
she remembers. If the patient misses 2 consecutive white tablets in Week 1 or
Week 2, the patient should take 2 tablets the day she remembers and 2 tablets
the next day; thereafter, the patient should resume taking 1 tablet daily until
she finishes the cycle pack. The patient should be instructed to use a back-up
method of birth control if she has intercourse in the 7 days after missing
pills. If the patient misses 2 consecutive white tablets in the third week or
misses 3 or more white tablets in a row at any time during the cycle, the
patient should keep taking 1 white tablet daily until the next Sunday. On Sunday
the patient should throw out the rest of that cycle pack and start a new cycle
pack that same day. The patient should be instructed to use a back-up method of
birth control if she has intercourse in the 7 days after missing pills.

DAY 1 START

Counting the first day of menstruation as “Day 1”, tablets are taken without
interruption as follows: One white tablet daily for 21 days, one light-green
(inert) tablet daily for 2 days followed by 1 yellow (ethinyl estradiol) tablet
daily for 5 days. For all subsequent cycles, the patient then begins a new
28-tablet regimen on the next day after taking the last yellow tablet. [If
switching directly from another oral contraceptive, the first white tablet
should be taken on the first day of menstruation which begins after the last
ACTIVE tablet of the previous product.]

If a patient misses 1 white tablet, she should take the missed tablet as soon as
she remembers. If the patient misses 2 consecutive white tablets in Week 1 or
Week 2, the patient should take 2 tablets the day she remembers and 2 tablets
the next day; thereafter, the patient should resume taking 1 tablet daily until
she finishes the cycle pack. The patient should be instructed to use a back-up
method of birth control if she has intercourse in the 7 days after missing
pills. If the patient misses 2 consecutive white tablets in the third week or if
the patient misses 3 or more white tablets in a row at any time during the
cycle, the patient should throw out the rest of that cycle pack and start a new
cycle pack that same day. The patient should be instructed to use a back-up
method of birth control if she has intercourse in the 7 days after missing
pills.

ALL ORAL CONTRACEPTIVES

Breakthrough bleeding, spotting, and amenorrhea are frequent reasons for
patients discontinuing oral contraceptives. In breakthrough bleeding, as in all
cases of irregular bleeding from the vagina, non­functional causes should be
borne in mind. In undiagnosed persistent or recurrent abnormal bleeding from the
vagina, adequate diagnostic measures are indicated to rule out pregnancy or
malignancy. If both pregnancy and pathology have been excluded, time or a change
to another preparation may solve the problem. Changing to an oral contraceptive
with a higher estrogen content, while potentially useful in minimizing menstrual
irregularity, should be done only if necessary since this may increase the risk
of thromboembolic disease.

Use of oral contraceptives in the event of a missed menstrual period:

 1. 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
    oral contraceptive use should be discontinued until pregnancy is ruled out.
 2. If the patient has adhered to the prescribed regimen and misses two
    consecutive periods, pregnancy should be ruled out before continuing oral
    contraceptive use.


HOW SUPPLIED

Mircette (desogestrel/ethinyl estradiol and ethinyl estradiol) Tablets contain
21 round white tablets, 2 round green tablets and 5 round yellow tablets in a
blister card within a recyclable plastic dispenser. Each white tablet (debossed
with “ dp” on one side and “021” on the other side) contains 0.15 mg desogestrel
and 0.02 mg ethinyl estradiol. Each green tablet (debossed with “ dp” on one
side and “331” on the other side) contains inert ingredients. Each yellow tablet
(debossed with “dp” on one side and “457” on the other side) contains 0.01 mg
ethinyl estradiol.

Boxes of 6 NDC 51285-114-58

Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature].

REFERENCES

1. Hatcher RA, Trussell J, Stewart F et al. Contraceptive Technology:
Seventeenth Revised Edition, New York: Irvington Publishers, 1998, in press.

2. Stadel BV. Oral contraceptives and cardiovascular disease. (Pt. 1). N Engl J
Med 1981; 305:612–618.

3. Stadel BV. Oral contraceptives and cardiovascular disease. (Pt. 2). N Engl J
Med 1981; 305:672–677.

36. 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; 315:405–411.

37. Pike MC, Henderson BE, Krailo MD, Duke A, Roy S. Breast cancer risk in young
women and use of oral contraceptives: possible modifying effect of formulation
and age at use. Lancet 1983; 2:926–929.

38. Paul C, Skegg DG, Spears GFS, Kaldor JM. Oral contraceptives and breast
cancer: A national study. Br Med J 1986; 293:723–725.

39. Miller DR, Rosenberg L, Kaufman DW, Schottenfeld D, Stolley PD, Shapiro S.
Breast cancer risk in relation to early oral contraceptive use. Obstet Gynecol
1986; 68:863–868.

40. Olson H, Olson KL, Moller TR, Ranstam J, Holm P. Oral contraceptive use and
breast cancer in young women in Sweden (letter). Lancet 1985; 2:748–749.

41. McPherson K, Vessey M, Neil A, Doll R, Jones L, Roberts M. Early
contraceptive use and breast cancer: Results of another case-control study. Br J
Cancer 1987; 56:653–660.

42. Huggins GR, Zucker PF. Oral contraceptives and neoplasia: 1987 update.
Fertil Steril 1987; 47:733–761.

46. Vessey MP, Lawless M, McPherson K, Yeates D. Neoplasia of the cervix uteri
and contraception: a possible adverse effect of the pill. Lancet 1983; 2:930.

47. Brinton LA, Huggins GR, Lehman HF, Malli K, Savitz DA, Trapido E, Rosenthal
J, Hoover R. Long-term use of oral contraceptives and risk of invasive cervical
cancer. Int J Cancer 1986; 38:339–344.

52. Henderson BE, Preston-Martin S, Edmondson HA, Peters RL, Pike MC.
Hepatocellular carcinoma and oral contraceptives. Br J Cancer 1983;
48:437–440.

53. Neuberger J, Forman D, Doll R, Williams R. Oral contraceptives and
hepatocellular carcinoma. Br Med J 1986; 292:1355–1357.

54. Forman D, Vincent TJ, Doll R. Cancer of the liver and oral contraceptives.
Br Med J 1986; 292:1357–1361.

79. Schlesselman J, Stadel BV, Murray P, Lai S. Breast Cancer in relation to
early use of oral contraceptives 1988; 259:1828–1833.

80. Hennekens CH, Speizer FE, Lipnick RJ, Rosner B, Bain C, Belanger C, Stampfer
MJ, Willett W, Peto R. A case-controlled study of oral contraceptive use and
breast cancer. JNCI 1984; 72:39–42.

81. LaVecchia C, Decarli A, Fasoli M, Franceschi S, Gentile A, Negri E,
Parazzini F, Tognoni G. Oral contraceptives and cancers of the breast and of the
female genital tract. Interim results from a case-control study. Br. J. Cancer
1986; 54:311–317.

82. Meirik O, Lund E, Adami H, Bergstrom R, Christoffersen T, Bergsjo P. Oral
contraceptive use in breast cancer in young women. A Joint National Case-control
study in Sweden and Norway. Lancet 1986; 11:650–654.

83. Kay CR, Hannaford PC. Breast cancer and the pill—A further report from the
Royal College of General Practitioners’ oral contraception study. Br. J.
Cancer 1988; 58:675–680.

84. Stadel BV, Lai S, Schlesselman JJ, Murray P. Oral contraceptives and
premenopausal breast cancer in nulliparous women. Contraception 1988;
38:287–299.

85. Miller DR, Rosenberg L, Kaufman DW, Stolley P, Warshauer ME, Shapiro S.
Breast cancer before age 45 and oral contraceptive use: New Findings. Am. J.
Epidemiol 1989; 129:269–280.

86. The UK National Case-Control Study Group, Oral contraceptive use and breast
cancer risk in young women. Lancet 1989; 1:973–982.

87. Schlesselman JJ. Cancer of the breast and reproductive tract in relation to
use of oral contraceptives. Contraception 1989; 40:1–38.

88. Vessey MP, McPherson K, Villard-Mackintosh L, Yeates D. Oral contraceptives
and breast cancer: latest findings in a large cohort study. Br. J. Cancer 1989;
59:613–617.

89. Jick SS, Walker AM, Stergachis A, Jick H. Oral contraceptives and breast
cancer. Br. J. Cancer 1989; 59:618–621.

90. Godsland, I et al. The effects of different formulations of oral
contraceptive agents on lipid and carbohydrate metabolism. N Engl J Med 1990;
323:1375–81.

93. Data on file, Organon Inc.

94. Fotherby, K. Oral contraceptives, lipids and cardiovascular diseases.
Contraception, 1985; Vol. 31; 4:367–94.

95. Lawrence, DM et al. Reduced sex hormone binding globulin and derived free
testosterone levels in women with severe acne. Clinical Endocrinology, 1981;
15:87–91.

105. Christensen J, Petrenaite V, Atterman J, et al. Oral contraceptives induce
lamotrigine metabolism: evidence from a doubleblind,placebo-controlled trial.
Epilepsia 2007;48(3):484­489.

Manufactured for: Teva Pharmaceuticals Parsippany, NJ 07054. Revised Jan 2023




SIDE EFFECTS FOR MIRCETTE

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

 * Thrombophlebitis and venous thrombosis with or without embolism
 * Arterial thromboembolism
 * Pulmonary embolism
 * Myocardial infarction
 * Cerebral hemorrhage
 * Cerebral thrombosis
 * Hypertension
 * Gallbladder disease
 * Hepatic adenomas or benign liver tumors

POST MARKETING EXPERIENCE

Five studies that compared breast cancer risk between ever-users (current or
past use) of COCs and never-users of COCs reported no association between ever
use of COCs and breast cancer risk, with effect estimates ranging from 0.90
-1.12 (Figure 2) (64-68).

Three studies compared breast cancer risk between current or recent COC users
(<6 months since last use) and never users of COCs (Figure 2) (64, 67,69). One
of these studies reported no association between breast cancer risk and COC use.
The other two studies found an increased relative risk of 1.19 -1.33 with
current or recent use. Both of these studies found an increased risk of breast
cancer with current use of longer duration, with relative risks ranging from
1.03 with less than one year of COC use to approximately 1.4 with more than 8-10
years of COC use.

FIGURE 2: RELEVANT STUDIES OF RISK OF BREAST CANCER WITH COMBINED ORAL
CONTRACEPTIVES





RR = relative risk; OR = odds ratio; HR = hazard ratio. “ever COC” are females
with current or past COC use; “never COC use” are females that never used COCs.

There is evidence of an association between the following conditions and the use
of oral contraceptives:

 * Mesenteric Thrombosis
 * Retinal thrombosis

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

 * Nausea
 * Vomiting
 * Gastrointestinal symptoms (such as abdominal cramps and bloating)
 * Breakthrough bleeding
 * Spotting
 * Change in menstrual flow
 * Amenorrhea
 * Temporary infertility after discontinuation of treatment
 * Edema
 * Melasma which may persist
 * Breast changes: tenderness, enlargement, secretion
 * Change in weight (increase or decrease)
 * Change in cervical erosion and secretion
 * Diminution in lactation when given immediately postpartum
 * Cholestatic jaundice
 * Migraine
 * Rash (allergic)
 * Mental depression
 * Reduced tolerance to carbohydrates
 * Vaginal candidiasis
 * Change in corneal curvature (steepening)
 * Intolerance to contact lenses

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

 * Pre-menstrual syndrome
 * Cataracts
 * Changes in appetite
 * Cystitis-like syndrome
 * Headache
 * Nervousness
 * Dizziness
 * Hirsutism
 * Loss of scalp hair
 * Erythema multiforme
 * Erythema nodosum
 * Hemorrhagic eruption
 * Vaginitis
 * Porphyria
 * Impaired renal function
 * Hemolytic uremic syndrome
 * Acne
 * Changes in libido
 * Colitis
 * Budd-Chiari Syndrome


DRUG INTERACTIONS FOR MIRCETTE

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 with barbiturates,
phenylbutazone, phenytoin sodium, carbamazepine and possibly with griseofulvin,
ampicillin, and tetracyclines (72).

Combined hormonal contraceptives have been shown to significantly decrease
plasma concentrations of lamotrigine when co-administered, likely due to
induction of lamotrigine glucuronidation. This may reduce seizure control;
therefore, dosage adjustments of lamotrigine may be necessary.

CONCOMITANT USE WITH HEPATITIS C VIRUS (HCV) COMBINATION THERAPY - LIVER ENZYME
ELEVATION

Co-administration of Mircette with HCV drug combinations containing
ombitasvir/paritaprevir/ritonavir, with or without dasabuvir is contraindicated
due to potential for ALT elevations (see CONTRAINDICATIONS and WARNINGS, RISK OF
LIVER ENZYME ELEVATIONS WITH CONCOMITANT HEPATITIS C TREATMENT).
Co-administration of Mircette and glecaprevir/pibrentasvir is not recommended
due to potential for ALT elevations.

Consult the labeling of the concurrently-used drug to obtain further information
about interactions with hormonal contraceptives or the potential for enzyme
alterations.

INTERACTIONS WITH LABORATORY TESTS

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; however, free or biologically active levels
    either decrease or remain unchanged.
 e. High-density lipoprotein cholesterol (HDL-C) and triglycerides may be
    increased, while low-density lipoprotein cholesterol (LDL-C) and total
    cholesterol (Total-C) may be decreased or unchanged.
 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.

REFERENCES

64. Strom BL, Tamragouri RT, Morse ML, Lazar EL, West SL, Stolley PD, Jones JK.
Oral contraceptives and other risk factors for gallbladder disease. Clin
Pharmacol Ther 1986; 39:335–341.

65. Wynn V, Adams PW, Godsland IF, Melrose J, Niththyananthan R, Oakley NW,
Seedj A. Comparison of effects of different combined oral-contraceptive
formulations on carbohydrate and lipid metabolism. Lancet 1979; 1:1045–1049.

66. Wynn V. Effect of progesterone and progestins on carbohydrate metabolism. In
Progesterone and Progestin. Edited by Bardin CW, Milgrom E, Mauvis-Jarvis P. New
York, Raven Press, 1983 pp. 395–410.

67. Perlman JA, Roussell-Briefel RG, Ezzati TM, Lieberknecht G. Oral glucose
tolerance and the potency of oral contraceptive progestogens. J Chronic Dis
1985; 38:857– 864.

68. Royal College of General Practitioners’ Oral Contraception Study: Effect on
hypertension and benign breast disease of progestogen component in combined oral
contraceptives. Lancet 1977; 1:624.

69. Fisch IR, Frank J. Oral contraceptives and blood pressure. JAMA 1977;
237:2499–2503.

72. Stockley I. Interactions with oral contraceptives. J Pharm 1976;
216:140-143.




WARNINGS FOR MIRCETTE

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 risks of several
serious conditions including myocardial infarction, thromboembolism, stroke,
hepatic neoplasia, and gallbladder disease, 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 principally based on studies
carried out in patients who used oral contraceptives with formulations of higher
doses of estrogens and progestogens than those in common use today. The effect
of long-term use of the oral contraceptives with formulations of lower doses 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
non-users. 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 non-users. The attributable risk does provide information about the
actual occurrence of a disease in the population (Adapted from refs. 2 and 3
with the author's permission). For further information, the reader is referred
to a text on epidemiologic methods.

THROMBOEMBOLIC DISORDERS AND OTHER VASCULAR PROBLEMS

THROMBOEMBOLISM

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 non-users to be 3 for the first episode
of superficial venous thromboembolic disease, 4 to 11 for deep vein thrombosis
or pulmonary embolism, and 1.5 to 6 for women with predisposing conditions for
venous thromboembolic disease (2,3,19–24). 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 (25). The risk of thromboembolic disease
associated with oral contraceptives is not related to length of use and
disappears after pill use is stopped (2).

Several epidemiologic studies indicate that third generation oral
contraceptives, including those containing desogestrel, are associated with a
higher risk of venous thromboembolism than certain second generation oral
contraceptives (102–104). In general, these studies indicate an approximate
two-fold increased risk, which corresponds to an additional 1 to 2 cases of
venous thromboembolism per 10,000 women-years of use. However, data from
additional studies have not shown this two-fold increase in risk.

A two- to four-fold increase in relative risk of post-operative thromboembolic
complications has been reported with the use of oral contraceptives (9,26). The
relative risk of venous thrombosis in women who have predisposing conditions is
twice that of women without such medical conditions (9,26). If feasible, oral
contraceptives should be discontinued 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
weeks after delivery in women who elect not to breast-feed.

MYOCARDIAL INFARCTION

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
(4–10). The risk is very low in women under the age of 30.

Smoking in combination with oral contraceptive use has been shown to contribute
substantially to the incidence of myocardial infarction in women in their
mid-thirties or older with smoking accounting for the majority of excess cases
(11). 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: CIRCULATORY DISEASE MORTALITY RATES PER 100,000 WOMANYEARS BY AGE,
SMOKING STATUS, AND ORAL CONTRACEPTIVE USE







Adapted from P.M. Layde and V. Beral, ref. #12.

Oral contraceptives may compound the effects of well-known risk factors, such as
hypertension, diabetes, hyperlipidemias, age and obesity (13). In particular,
some progestogens are known to decrease HDL cholesterol and cause glucose
intolerance, while estrogens may create a state of hyperinsulinism (14–18). 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.

CEREBROVASCULAR DISEASES

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 non-users, for both types of strokes, while smoking
interacted to increase the risk for hemorrhagic strokes (27–29).

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
(30). The relative risk of hemorrhagic stroke is reported to be 1.2 for
non-smokers 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 (30). The
attributable risk is also greater in older women (3).

DOSE-RELATED RISK OF VASCULAR DISEASE FROM ORAL CONTRACEPTIVES

A positive association has been observed between the amount of estrogen and
progestogen in oral contraceptives and the risk of vascular disease (31–33). A
decline in serum high-density lipoproteins (HDL) has been reported with many
progestational agents (14–16). 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 progestogens used in the contraceptives. 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 0.035 mg or less of estrogen.

PERSISTENCE OF RISK OF VASCULAR DISEASE

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 40 to 49 years old who had used oral
contraceptives for five or more years, but this increased risk was not
demonstrated in other age groups (8). 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
(34). However, both studies were performed with oral contraceptive formulations
containing 50 micrograms or more of estrogen.

ESTIMATES OF MORTALITY FROM CONTRACEPTIVE USE

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 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 (35). However, current clinical practice involves the use of lower
estrogen formulations combined with careful consideration of risk factors.

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 (100,101), 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 non-smoking women
(even with the newer low-dose formulations), there are also 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 low-dose oral
contraceptive use by healthy non-smoking 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 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 methodsa 7 7.4 9.1 14.8 25.7 28.2 Oral contraceptives non-smokerb 0.3
0.5 0.9 1.9 13.8 31.6 Oral contraceptives Smokerb 2.2 3.4 6.6 13.5 51.1 117.2
IUDb 0.8 0.8 1 1 1.4 1.4 Condoma 1.1 1.6 0.7 0.2 0.3 0.4 Diaphragm/spermicidea
1.9 1.2 1.2 1.3 2.2 2.8 Periodic abstinencea 2.5 1.6 1.6 1.7 2.9 3.6 Adapted
from H.W. Ory, ref. #35.
a Deaths are birth related
b Deaths are method related



CARCINOMA OF THE REPRODUCTIVE ORGANS AND BREASTS

Numerous epidemiologic 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. Some studies have reported an increased relative risk
of developing breast cancer, particularly at a younger age. This increased
relative risk appears to be related to duration of use (36–43, 79–89).

Some studies suggest that oral contraceptive use has been associated with an
increase in the risk of cervical intra-epithelial neoplasia in some populations
of women (45–48). However, there continues to be controversy about the extent to
which such findings may be due to differences in sexual behavior and other
factors.

HEPATIC NEOPLASIA

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 especially with
oral contraceptives of higher dose (49). Rupture of rare, benign, hepatic
adenomas may cause death through intra-abdominal hemorrhage (50,51).

Studies from Britain have shown an increased risk of developing hepatocellular
carcinoma (52– 54) in long-term (>8 years) oral contraceptive users. However,
these cancers are extremely rare in the US and the attributable risk (the excess
incidence) of liver cancers in oral contraceptive users approaches less than one
per million users.

OCULAR LESIONS

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.

ORAL CONTRACEPTIVE USE BEFORE OR DURING EARLY PREGNANCY

Extensive epidemiologic studies have revealed no increased risk of birth defects
in women who have used oral contraceptives prior to pregnancy (55–57). Studies
also do not suggest a teratogenic effect, particularly in so far as cardiac
anomalies and limb reduction defects are concerned (55,56,58,59), when oral
contraceptives are 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 first missed period. Oral contraceptive use should be
discontinued until pregnancy is ruled out.

GALLBLADDER DISEASE

Earlier studies have reported an increased lifetime relative risk of gallbladder
surgery in users of oral contraceptives and estrogens (60,61). More recent
studies, however, have shown that the relative risk of developing gallbladder
disease among oral contraceptive users may be minimal (62–64). The recent
findings of minimal risk may be related to the use of oral contraceptive
formulations containing lower hormonal doses of estrogens and progestogens.

CARBOHYDRATE AND LIPID METABOLIC EFFECTS

Oral contraceptives have been shown to cause a decrease in glucose tolerance in
a significant percentage of users (17). Oral contraceptives containing greater
than 75 micrograms of estrogens cause hyperinsulinism, while lower doses of
estrogen cause less glucose intolerance (65). Progestogens increase insulin
secretion and create insulin resistance, this effect varying with different
progestational agents (17,66). However, in the non-diabetic woman, oral
contraceptives appear to have no effect on fasting blood glucose (67). Because
of these demonstrated effects, prediabetic and diabetic women should be
carefully monitored 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.

ELEVATED BLOOD PRESSURE

An increase in blood pressure has been reported in women taking oral
contraceptives (68) and this increase is more likely in older oral contraceptive
users (69) and with continued use (61). Data from the Royal College of General
Practitioners (12) and subsequent randomized trials have shown that the
incidence of hypertension increases with increasing quantities of progestogens.

Women with a history of hypertension or hypertension-related diseases, or renal
disease (70) should be encouraged to use another method of contraception. If
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 (69), and there is no difference in the
occurrence of hypertension between ever- and never-users (68,70,71).

HEADACHE

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.

BLEEDING IRREGULARITIES

Breakthrough bleeding and spotting are sometimes encountered in patients on oral
contraceptives, especially during the first three months of use. Non-hormonal
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.

ECTOPIC PREGNANCY

Ectopic as well as intrauterine pregnancy may occur in contraceptive failures.


PRECAUTIONS FOR MIRCETTE

GENERAL

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

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.

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.

LIVER FUNCTION

If jaundice develops in any woman receiving such drugs, the medication should be
discontinued. Steroid hormones may be poorly metabolized in patients with
impaired liver function.

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 which might be aggravated by fluid retention.

EMOTIONAL DISORDERS

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

CONTACT LENSES

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

CARCINOGENESIS

See WARNINGS section.

PREGNANCY

Pregnancy Category X (see CONTRAINDICATIONS and WARNINGS sections).

NURSING MOTHERS

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.

PEDIATRIC USE

Safety and efficacy of Mircette® (desogestrel/ethinyl estradiol and ethinyl
estradiol) Tablets have 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.

INFORMATION FOR THE PATIENT

See Patient Labeling

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66. Wynn V. Effect of progesterone and progestins on carbohydrate metabolism. In
Progesterone and Progestin. Edited by Bardin CW, Milgrom E, Mauvis-Jarvis P. New
York, Raven Press, 1983 pp. 395–410.

67. Perlman JA, Roussell-Briefel RG, Ezzati TM, Lieberknecht G. Oral glucose
tolerance and the potency of oral contraceptive progestogens. J Chronic Dis
1985; 38:857–864.

68. Royal College of General Practitioners' Oral Contraception Study: Effect on
hypertension and benign breast disease of progestogen component in combined oral
contraceptives. Lancet 1977;

 69. Fisch IR, Frank J. Oral contraceptives and blood pressure. JAMA 1977;
237:2499– 2503.

70. Laragh AJ. Oral contraceptive induced hypertension—nine years later. Am J
Obstet Gynecol 1976; 126:141–147.

71. Ramcharan S, Peritz E, Pellegrin FA, Williams WT. Incidence of hypertension
in the Walnut Creek Contraceptive Drug Study cohort. In Pharmacology of Steroid
Contraceptive Drugs. Garattini S, Berendes HW. Eds. New York, Raven Press, 1977
pp. 277–288. (Monographs of the Mario Negri Institute for Pharmacological
Research, Milan).

73. 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 ovarian cancer. JAMA 1983; 249:1596–1599.

79. Schlesselman J, Stadel BV, Murray P, Lai S. Breast Cancer in relation to
early use of oral contraceptives 1988; 259:1828–1833.

80. Hennekens CH, Speizer FE, Lipnick RJ, Rosner B, Bain C, Belanger C, Stampfer
MJ, Willett W, Peto R. A case-controlled study of oral contraceptive use and
breast cancer. JNCI 1984; 72:39–42.

81. LaVecchia C, Decarli A, Fasoli M, Franceschi S, Gentile A, Negri E,
Parazzini F, Tognoni G. Oral contraceptives and cancers of the breast and of the
female genital tract. Interim results from a case-control study. Br. J. Cancer
1986; 54:311–317.

 82. Meirik O, Lund E, Adami H, Bergstrom R, Christoffersen T, Bergsjo P. Oral
contraceptive use in breast cancer in young women. A Joint National Case-control
study in Sweden and Norway. Lancet 1986; 11:650–654.

83. Kay CR, Hannaford PC. Breast cancer and the pill—A further report from the
Royal College of General Practitioners' oral contraception study. Br. J. Cancer
1988; 58:675–680.

84. Stadel BV, Lai S, Schlesselman JJ, Murray P. Oral contraceptives and
premenopausal breast cancer in nulliparous women. Contraception 1988;
38:287–299.

85. Miller DR, Rosenberg L, Kaufman DW, Stolley P, Warshauer ME, Shapiro S.
Breast cancer before age 45 and oral contraceptive use: New Findings. Am. J.
Epidemiol 1989; 129:269–280.

86. The UK National Case-Control Study Group, Oral contraceptive use and breast
cancer risk in young women. Lancet 1989; 1:973–982.

87. Schlesselman JJ. Cancer of the breast and reproductive tract in relation to
use of oral contraceptives. Contraception 1989; 40:1–38.

88. Vessey MP, McPherson K, Villard-Mackintosh L, Yeates D. Oral contraceptives
and breast cancer: latest findings in a large cohort study. Br. J. Cancer 1989;
59:613–617.

89. Jick SS, Walker AM, Stergachis A, Jick H. Oral contraceptives and breast
cancer. Br. J. Cancer 1989; 59:618–621.

100. Porter JB, Hunter J, Jick H et al. Oral contraceptives and nonfatal
vascular disease. Obstet Gynecol 1985; 66:1–4.

101. Porter JB, Jick H, Walker AM. Mortality among oral contraceptive users.
Obstet Gynecol 1987; 7029–32.

102. Jick H, Jick SS, Gurewich V, Myers MW, Vasilakis C. Risk of idiopathic
cardiovascular death and non-fatal venous thromboembolism in women using oral
contraceptives with differing progestagen components. Lancet, 1995; 346:1589–93.

103. World Health Organization Collaborative Study of Cardiovascular Disease and
Steroid Hormone Contraception. Effect of different progestagens in low oestrogen
oral contraceptives on venous thromboembolic disease. Lancet, 1995; 346:1582–88.

104. Spitzer WO, Lewis MA, Heinemann LAJ, Thorogood M, MacRae KD on behalf of
Transnational Research Group on Oral Contraceptives and Health of Young Women.
Third generation oral contraceptives and risk of venous thromboembolic
disorders: An international case-control study. Br Med J, 1996; 312:83–88.

105. Christensen J, Petrenaite V, Atterman J, et al. Oral contraceptives induce
lamotrigine metabolism: evidence from a doubleblind,placebo-controlled trial.
Epilepsia 2007;48(3):484-489.


OVERDOSE INFORMATION FOR MIRCETTE

Serious ill effects have not been reported following acute ingestion of large
doses of oral contraceptives by young children. Overdosage may cause nausea, and
withdrawal bleeding may occur in females.

NON-CONTRACEPTIVE HEALTH BENEFITS

The following non-contraceptive health benefits related to the use of oral
contraceptives are supported by epidemiologic studies which largely utilized
oral contraceptive formulations containing estrogen doses exceeding 0.035 mg of
ethinyl estradiol or 0.05 mg of mestranol (73–78).

EFFECTS ON MENSES

 * increased menstrual cycle regularity
 * decreased blood loss and decreased incidence of iron deficiency anemia
 * decreased incidence of dysmenorrhea

EFFECTS RELATED TO INHIBITION OF OVULATION

 * decreased incidence of functional ovarian cysts
 * decreased incidence of ectopic pregnancies

EFFECTS FROM LONG-TERM USE:

 * decreased incidence of fibroadenomas and fibrocystic disease of the breast
 * decreased incidence of acute pelvic inflammatory disease
 * decreased incidence of endometrial cancer
 * decreased incidence of ovarian cancer


CONTRAINDICATIONS FOR MIRCETTE

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

 * Thrombophlebitis or thromboembolic disorders
 * A past history of deep vein thrombophlebitis or thromboembolic disorders
 * Cerebral vascular or coronary artery disease
 * Current diagnosis of, or history of, breast cancer, which may be
   hormone-sensitive
 * Undiagnosed abnormal genital bleeding
 * Cholestatic jaundice of pregnancy or jaundice with prior pill use
 * Hepatic adenomas or carcinomas
 * Are receiving Hepatitis C drug combinations containing
   ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, due to the
   potential for ALT elevations (see WARNINGS, RISK OF LIVER ENZYME ELEVATIONS
   WITH CONCOMITANT HEPATITIS C TREATMENT)

REFERENCES

73. 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 ovarian cancer. JAMA 1983; 249:1596–1599.

74. The Cancer and Steroid Hormone Study of the Centers for Disease Control and
the National Institute of Child Health and Human Development: Combination oral
contraceptive use and the risk of endometrial cancer. JAMA 1987; 257:796–800.

75. Ory HW. Functional ovarian cysts and oral contraceptives: negative
association confirmed surgically. JAMA 1974; 228:68–69.

76. Ory HW, Cole P, Macmahon B, Hoover R. Oral contraceptives and reduced risk
of benign breast disease. N Engl J Med 1976; 294:419–422.

77. Ory HW. The noncontraceptive health benefits from oral contraceptive use.
Fam Plann Perspect 1982; 14:182–184.

78. Ory HW, Forrest JD, Lincoln R. Making Choices: Evaluating the health risks
and benefits of birth control methods. New York, The Alan Guttmacher Institute,
1983; p. 1.




CLINICAL PHARMACOLOGY FOR MIRCETTE

Combination oral contraceptives 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 increase the difficulty
of sperm entry into the uterus) and the endometrium (which reduce the likelihood
of implantation).

Receptor binding studies, as well as studies in animals, have shown that
etonogestrel, the biologically active metabolite of desogestrel, combines high
progestational activity with minimal intrinsic androgenicity (91,92). The
relevance of this latter finding in humans is unknown.

PHARMACOKINETICS

ABSORPTION

Desogestrel is rapidly and almost completely absorbed and converted into
etonogestrel, its biologically active metabolite. Following oral administration,
the relative bioavailability of desogestrel compared to a solution, as measured
by serum levels of etonogestrel, is approximately 100%. Mircette
(desogestrel/ethinyl estradiol and ethinyl estradiol) Tablets provide two
different regimens of ethinyl estradiol; 0.02 mg in the combination tablet
[white] as well as 0.01 mg in the yellow tablet. Ethinyl estradiol is rapidly
and almost completely absorbed. After a single dose of Mircette combination
tablet [white], the relative bioavailability of ethinyl estradiol is
approximately 93% while the relative bioavailability of the 0.01 mg tablet
[yellow] is 99%. The effect of food on the bioavailability of Mircette tablets
following oral administration has not been evaluated.

The pharmacokinetics of etonogestrel and ethinyl estradiol following multiple
dose administration of Mircette tablets were determined during the third cycle
in 17 subjects. Plasma concentrations of etonogestrel and ethinyl estradiol
reached steady-state by Day 21. The AUC(0–24) for etonogestrel at steady-state
on Day 21 was approximately 2.2 times higher than AUC(0–24) on Day 1 of the
third cycle. The pharmacokinetic parameters of etonogestrel and ethinyl
estradiol during the third cycle following multiple dose administration of
Mircette tablets are summarized in Table I.

TABLE I: MEAN (SD) PHARMACOKINETIC PARAMETERS OF Mircett® OVER A 28-DAY DOSING
PERIOD IN THE THIRD CYCLE (n=17). Etonogestrel

Day Doseamg Cmax pg/mL Tmax h t½ h AUC0-24 pg/mL•hr CL/F L/h 1 0.15 2503.6
(987.6) 2.4 (1.0) 29.8 (16.3) 17,832 (5674) 5.4 (2.5) 21 0.15 4091.2 (1186.2)
1.6 (0.7) 27.8 (7.2) 39,391 (12,134) 4.4 (1.4) a) Desogestrel



Ethinyl Estradiol

Day Dose mg Cmax pg/mL Tmax h t½ h AUC0-24 pg/mL•hr CL/F L/h 1 0.02 51.9 (15.4)
2.9 (1.2) 16.5 (4.8) 566 (173)a 25.7 (9.1) 21 0.02 62.2 (25.9) 2.0 (0.8) 23.9
(25.5) 597 (127)a 35.1 (8.2) 24 0.01 24.6 (10.8) 2.4 (1.0) 18.8 (10.3) 246 (65)
43.6 (12.2) 28 0.01 35.3 (27.5) 2.1 (1.3) 18.9 (8.3) 312 (62) 33.2 (6.6) Cmax
– measured peak concentration
Tmax – observed time of peak concentration
t½ – elimination half-life, calculated by 0.693/Kelim
AUC0–24 – area under the concentration-time curve calculated by the linear
trapezoidal rule (Time 0 to 24 hours)
CL/F – apparent clearance
a) n=16



DISTRIBUTION

Etonogestrel, the active metabolite of desogestrel, was found to be 99% protein
bound, primarily to sex hormone-binding globulin (SHBG). Ethinyl estradiol is
approximately 98.3% bound, mainly to plasma albumin. Ethinyl estradiol does not
bind to SHBG, but induces SHBG synthesis. Desogestrel, in combination with
ethinyl estradiol, does not counteract the estrogen-induced increase in SHBG,
resulting in lower serum levels of free testosterone (96–99).

METABOLISM

Desogestrel

Desogestrel is rapidly and completely metabolized by hydroxylation in the
intestinal mucosa and on first pass through the liver to etonogestrel. Other
metabolites (i.e., 3α-OH-desogestrel, 3β-OH-desogestrel, and
3α-OH-5α-H-desogestrel) with no pharmacologic actions also have been identified
and these metabolites may undergo glucuronide and sulfate conjugation.

Ethinyl Estradiol

Ethinyl estradiol is subject to a significant degree of presystemic conjugation
(phase II metabolism). Ethinyl estradiol escaping gut wall conjugation undergoes
phase I metabolism and hepatic conjugation (phase II metabolism). Major phase I
metabolites are 2-OH-ethinyl estradiol and 2-methoxy-ethinyl estradiol. Sulfate
and glucuronide conjugates of both ethinyl estradiol and phase I metabolites,
which are excreted in bile, can undergo enterohepatic circulation.

Excretion

Etonogestrel and ethinyl estradiol are excreted in urine, bile, and feces. At
steady state, on Day 21, the elimination half-life of etonogestrel is 27.8±7.2
hours and the elimination half-life of ethinyl estradiol for the combination
tablet is 23.9±25.5 hours. For the 0.01 mg ethinyl estradiol tablet [yellow],
the elimination half-life at steady state, Day 28, is 18.9±8.3 hours.

SPECIAL POPULATIONS

RACE

There is no information to determine the effect of race on the pharmacokinetics
of Mircette.

HEPATIC INSUFFICIENCY

No formal studies were conducted to evaluate the effect of hepatic disease on
the disposition of Mircette.

RENAL INSUFFICIENCY

No formal studies were conducted to evaluate the effect of renal disease on the
disposition of Mircette.

DRUG-DRUG INTERACTIONS

Interactions between desogestrel/ethinyl estradiol and other drugs have been
reported in the literature. No formal drug-drug interaction studies were
conducted (see PRECAUTIONS section).

REFERENCES

91. Kloosterboer, HJ et al. Selectivity in progesterone and androgen receptor
binding of progestogens used in oral contraception. Contraception, 1988;
38:325–32.

92. Van der Vies, J and de Visser, J. Endocrinological studies with desogestrel.
Arzneim. Forsch./Drug Res., 1983; 33(l),2:231–6.

96. Cullberg, G et al. Effects of a low-dose desogestrel-ethinyl estradiol
combination on hirsutism, androgens and sex hormone binding globulin in women
with a polycystic ovary syndrome. Acta Obstet Gynecol Scand, 1985; 64:195–202.

97. Jung-Hoffmann, C and Kuhl, H. Divergent effects of two low-dose oral
contraceptives on sex hormone-binding globulin and free testosterone. AJOG,
1987; 156:199–203.

98. Hammond, G et al. Serum steroid binding protein concentrations, distribution
of progestogens, and bioavailability of testosterone during treatment with
contraceptives containing desogestrel or levonorgestrel. Fertil. Steril., 1984;
42:44–51.

99. Palatsi, R et al. Serum total and unbound testosterone and sex hormone
binding globulin (SHBG) in female acne patients treated with two different oral
contraceptives. Acta Derm Venereol, 1984; 64:517–23.


PATIENT INFORMATION FOR MIRCETTE

Mircette®
(desogestrel/ethinyl estradiol and ethinyl estradiol) 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.

PLEASE NOTE: This labeling is revised from time to time as important new medical
information becomes available. Therefore, please review this labeling carefully.

DESCRIPTION

The following oral contraceptive product contains a combination of a progestin
and estrogen, the two kinds of female hormones:

Each white tablet contains 0.15 mg desogestrel and 0.02 mg ethinyl estradiol.
Each light-green tablet contains inert ingredients and each yellow tablet
contains 0.01 mg ethinyl estradiol.

INTRODUCTION

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
doctor or 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 doctor's or healthcare
provider's advice with regard to regular check-ups while you are on the pill.

EFFECTIVENESS OF ORAL CONTRACEPTIVES

Oral contraceptives or “birth control pills” or “the pill” are used to prevent
pregnancy and are more effective than other non-surgical methods of birth
control. When they are taken correctly, 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 5% 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:



Implants (2 or 6 capsules): <1% Male sterilization: <1% Injection: <1% Cervical
Cap with spermicides: 20 to 40% IUD: <1 to 2% Condom alone (male): 14% Diaphragm
with spermicides: 20% Condom alone (female): 21% Spermicides alone: 26% Periodic
abstinence: 25% Vaginal sponge: 20 to 40% Withdrawal: 19% Female sterilization:
<1% No methods: 85%.



WHO SHOULD NOT TAKE ORAL CONTRACEPTIVES

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 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:

 * A history of heart attack or stroke
 * Blood clots in the legs (thrombophlebitis), lungs (pulmonary embolism), or
   eyes
 * A history of blood clots in the deep veins of your legs
 * Chest pain (angina pectoris)
 * Known or suspected breast cancer or cancer of the lining of the uterus,
   cervix or vagina
 * Unexplained vaginal bleeding (until a diagnosis is reached by your doctor)
 * Yellowing of the whites of the eyes or of the skin (jaundice) during
   pregnancy or during previous use of the pill
 * Liver tumor (benign or cancerous)
 * Known or suspected pregnancy.

Tell your doctor or healthcare provider if you have ever had any of these
conditions. Your doctor or healthcare provider can recommend another method of
birth control.

OTHER CONSIDERATIONS BEFORE TAKING ORAL CONTRACEPTIVES

Tell your doctor or healthcare provider if you have:

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

Women with any of these conditions should be checked often by their doctor or
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.

RISKS OF TAKING ORAL CONTRACEPTIVES

1. Risk of developing blood clots

Blood clots and blockage of blood vessels are one of the most serious side
effects of taking oral contraceptives and can cause death or serious disability.
In particular, a clot in the leg can cause thrombophlebitis and a clot that
travels to the lungs can cause a sudden blockage of the vessel carrying blood to
the lungs. The risks of these side effects may be greater with
desogestrelcontaining oral contraceptives such as Mircette® than with certain
other low-dose pills. 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 or healthcare provider
about stopping oral contraceptives three to four weeks before surgery and not
taking oral contraceptives for two weeks after surgery or during bed rest. You
should also not take oral contraceptives soon after delivery of a baby. It is
advisable to wait for at least four weeks after delivery if you are not
breast-feeding or four weeks after a second trimester abortion. If you are
breast-feeding, you should wait until you have weaned your child before using
the pill (see 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 venous
thromboembolic disease associated with oral contraceptives does not increase
with length of use and disappears after pill use is stopped. The risk of
abnormal blood clotting increases with age in both users and non-users 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 non-users 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 non-users
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 or
rupture of blood vessels in the brain) and angina pectoris and heart attacks
(blockage of blood vessels in the heart). Any of these conditions can cause
death or serious disability.

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

3. Gallbladder disease

Oral contraceptive users probably have a greater risk than non-users 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 liver tumors can rupture and cause fatal internal bleeding. In
addition, a possible but not definite association has been found with the pill
and liver cancers in two studies, in which a few women who developed these very
rare cancers were found to have used oral contraceptives for long periods.
However, liver cancers are extremely rare. The chance of developing liver cancer
from using the pill is thus even rarer.

5. Cancer of the 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 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 NON-STERILE WOMEN, BY FERTILITY CONTROL METHOD
ACCORDING TO AGE


Method of control and outcome 15-19 20-24 25-29 30-34 35-39 40-44 No fertility
control methods * 7.0 7.4 9.1 14.8 25.7 28.2 Oral contraceptives non-smoker**
0.3 0.5 0.9 1.9 13.8 31.6 Oral contraceptives 2.2 3.4 6.6 13.5 51.1 117.2
Smoker** IUD** 0.8 0.8 1.0 1.0 1.4 1.4 Condom* 1.1 1.6 0.7 0.2 0.3 0.4
Diaphragm/spermicide* 1.9 1.2 1.2 1.3 2.2 2.8 Periodic abstinence* 2.5 1.6 1.6
1.7 2.9 3.6 * Deaths are birth related
** Deaths are method related



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

WARNING SIGNALS

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

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

SIDE EFFECTS OF ORAL CONTRACEPTIVES

1. Vaginal bleeding

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

2. Contact lenses

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

3. Fluid retention

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

4. Melasma

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

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 side effects bother you, call your doctor or healthcare
provider.

GENERAL PRECAUTIONS

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

There may be times when you may not menstruate regularly after you have
completed taking a cycle of pills. If you have taken your pills regularly and
miss one menstrual period, continue taking your pills for the next cycle but be
sure to inform your doctor or healthcare provider before doing so. If you have
not taken the pills daily as instructed and missed a menstrual period, or if you
missed two consecutive menstrual periods, you may be pregnant. Check with your
doctor or healthcare provider immediately to determine whether you are pregnant.
Do not continue to take oral contraceptives until you are sure you are not
pregnant, but continue to use another method of contraception.

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

2. While breast-feeding

If you are breast-feeding, consult your doctor or healthcare provider 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 or healthcare
provider 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), 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 which can make
oral contraceptives less effective.

Birth control pills may interact with lamotrigine, an anticonvulsant used for
epilepsy. This may increase the risk of seizures, so your physician may need to
adjust the dose of lamotrigine.

Some medicines may make birth control pill less effective, including:

 * Barbiturates
 * Bosentan
 * Carbamazepine
 * Felbamate
 * Griseofulvin
 * Oxcarbazepine
 * Phenytoin
 * Rifampin
 * St. John's wort
 * Topiramate

As with all prescription products, you should notify your healthcare provider of
any other medicines and herbal products you are taking. You may need to use a
barrier contraceptive when you take drugs or products that can make birth
control pills less effective.

5. Sexually transmitted diseases

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.

HOW TO TAKE THE PILL

IMPORTANT POINTS TO REMEMBER

BEFORE YOU START TAKING YOUR PILLS:

1. BE SURE TO READ THESE DIRECTIONS:

Before you start taking your pills.

Anytime you are not sure what to do.

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

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

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

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

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

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

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

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

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

6. IF YOU HAVE TROUBLE REMEMBERING TO TAKE THE PILL, talk to your doctor or
healthcare provider about how to make pill-taking easier or about using another
method of birth control.

7. IF YOU HAVE ANY QUESTIONS OR ARE UNSURE ABOUT THE INFORMATION IN THIS
LEAFLET, call your doctor or healthcare provider.

BEFORE YOU START TAKING YOUR PILLS

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

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

8. LOOK AT YOUR PILL PACK: IT WILL HAVE 28 PILLS:

This 28-pill pack has 26 “active” [white and yellow] pills (with hormones) and 2
“inactive” [light-green] pills (without hormones).

10. ALSO FIND:

1) where on the pack to start taking the pills,

2) in what order to take the pills (follow the arrows) and

3) the week numbers as shown in the picture below.







11. BE SURE YOU HAVE READY AT ALL TIMES:

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

AN EXTRA, FULL PILL PACK.

WHEN TO START THE FIRST PACK OF PILLS

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

DAY 1 START

12. Pick the day label strip that starts with the first day of your period (this
is the day you start bleeding or spotting, even if it is almost midnight when
the bleeding begins).

13. Place this day label strip in the cycle tablet dispenser over the area that
has the days of the week (starting with Sunday) imprinted.







Note: If the first day of your period is a Sunday, you can skip steps #1 and #2.

14. Take the first “active” [white] pill of the first pack during the first 24
hours of your period.

15. You will not need to use a back-up method of birth control, since you are
starting the pill at the beginning of your period.

SUNDAY START

16. Take the first “active” [white] pill of the first pack on the Sunday after
your period starts, even if you are still bleeding. If your period begins on
Sunday, start the pack that same day.

17. Use another method of birth control as a back-up method if you have sex
anytime from the Sunday you start your first pack until the next Sunday (7
days). Condoms, foam, or the sponge are good back-up methods of birth control.

WHAT TO DO DURING THE MONTH

18. 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.

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

21 pills: Wait 7 days to start the next pack. You will probably have your period
during that week. Be sure that no more than 7 days pass between 21-day packs.

28 pills: Start the next pack on the day after your last pill. Do not wait any
days between packs.

WHAT TO DO IF YOU MISS PILLS

If you MISS 1 “active” [white] pill:

20. Take it as soon as you remember. Take the next pill at your regular time.
This means you take 2 pills in 1 day.

21. You do not need to use a back-up birth control method if you have sex. If
you MISS 2 “active” [white] pills in a row in WEEK 1 OR WEEK 2 of your pack:

22. Take 2 pills on the day you remember and 2 pills the next day.

23. Then take 1 pill a day until you finish the pack.

24. 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 method for those 7 days.

If you MISS 2 “active” [white] pills in a row in WEEK 3:

25. If you are a Day 1 Starter:

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

If you are a Sunday Starter:

Keep taking 1 pill every day until Sunday.

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

26. You may not have your period this month but this is expected. However, if
you miss your period 2 months in a row, call your doctor or healthcare provider
because you might be pregnant.

27. You MAY BECOME PREGNANT if you have sex in the 7 days after you miss pills.
You MUST use another birth control method (such as condoms, foam, or sponge) as
a back-up method for those 7 days.

If you MISS 3 OR MORE “active” [white] pills in a row (during the first 3
weeks):

28. If you are a Day 1 Starter:

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

If you are a Sunday Starter:

Keep taking 1 pill every day until Sunday.

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

29. You may not have your period this month but this is expected. However, if
you miss your period 2 months in a row, call your doctor or healthcare provider
because you might be pregnant.

30. You MAY BECOME PREGNANT if you have sex in the 7 days after you miss pills.
You MUST use another birth control method (such as condoms, foam, or sponge) as
a back-up method for those 7 days.

A REMINDER FOR THOSE ON 28-DAY PACKS

If you forget any of the 2 [light-green] or 5 [yellow] pills in Week 4:

THROW AWAY the pills you missed.

Keep taking 1 pill each day until the pack is empty.

You do not need a back-up method.

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

Use a BACK-UP METHOD anytime you have sex.

KEEP TAKING ONE “ACTIVE” [WHITE] PILL EACH DAY until you can reach your doctor
or healthcare provider.

PREGNANCY DUE TO PILL FAILURE

The incidence of pill failure resulting in pregnancy is approximately one
percent (i.e., one pregnancy per 100 women per year) if taken every day as
directed, but more typical failure rates are about 5%. If failure does occur,
the risk to the fetus is minimal.

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 soon after stopping the pill.

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 doctor,
healthcare provider or pharmacist.

OTHER INFORMATION

Your doctor or 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 your doctor or the
healthcare provider believes that it is a good medical practice to postpone it.
You should be reexamined at least once a year. Be sure to inform your doctor or
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 doctor or
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.

HEALTH BENEFITS FROM ORAL CONTRACEPTIVES

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

 * menstrual cycles may become more regular.
 * blood flow during menstruation may be lighter and less iron may be lost.
   Therefore, anemia due to iron deficiency is less likely to occur.
 * pain or other symptoms during menstruation may be encountered less
   frequently.
 * ectopic (tubal) pregnancy may occur less frequently.
 * non-cancerous cysts or lumps in the breast may occur less frequently.
 * acute pelvic inflammatory disease may occur less frequently.
 * oral contraceptive use may provide some protection against developing two
   forms of cancer: cancer of the ovaries and cancer of the lining of the
   uterus.

If you want more information about birth control pills, ask your doctor,
healthcare provider, or pharmacist. They have a more technical leaflet called
the Prescribing Information which you may wish to read.


FROM

WOMEN'S HEALTH RESOURCES

 * Early Signs of Pregnancy
 * Your Birth Control Questions, Answered

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