Professional Drug Information > Yasmin

Drospirenone and Ethinyl Estradiol (Systemic)

VA CLASSIFICATION
Primary: HS104

Commonly used brand name(s): Yasmin.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Contraceptive, systemic —

Indications

Accepted

Pregnancy, prevention of—Combination drospirenone-ethinyl estradiol oral contraceptive is indicated for the prevention of pregnancy.
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Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Molecular weight—
    Drospirenone—366.5^{01}
    Ethinyl estradiol—296.4^{01}

Mechanism of action/Effect:

Contraceptive, systemic— Drospirenone and ethinyl estradiol act to suppress gonadatropins. This is achieved through inhibition of ovulation and alterations to both the cervical mucus and the endometrium.^{01}

Absorption:

Drospirenone and ethinyl estradiol combination— The absolute bioavailability of the drospirenone and ethinyl estradiol combination is unknown^{01}

Drospirenone— The absolute bioavailability of drospirenone is 76%^{01}

Ethinyl estradiol— The absolute bioavailability of ethinyl estradiol is 40%^{01}

Distribution:

Oral contraceptives are widely distributed^{01}

Drospirenone— Volume of distribution (Vol _D) is 4 liters (L) per kilogram (kg).^{01}

Ethinyl estradiol— Volume of distribution (Vol _D) is 4–5 liters per kilogram. ^{01}

Protein binding:

Drospirenone— Binds to serum proteins (97%) other than sex hormone binding globulin and corticosteroid binding globulin^{01}

Ethinyl estradiol— Highly but non-specificaly bound to serum albumin.^{01}

Half-life:

Drospirenone— 30 hours^{01}

Ethinyl estradiol— 24 hours^{01}

Elimination:
    Drospirenone— Excretion of drospirenone is nearly complete after 10 days and amounts excreted were slightly higher in feces compared to urine. It is highly metabolized and only trace amounts of unchanged drospirenone were excreted. 38 to 47% of the metabolites in urine were glucuronide and sulfate conjugates compared to 17 to 20% in feces.^{01}
    Ethinyl estradiol— Ethinyl estradiol is not excreted unchanged. It is excreted in the urine and feces as glucuronide and sulfate conjugates and undergoes enterohepatic circulation^{01}


Precautions to Consider

Carcinogenicity

A 24 month oral carcinogenicity study in mice dosed with 10 mg per kg per day drospirenone alone or 1 + 0.01, 3 + 0.03 and 10 + 0.1 mg per kg per day of drospirenone and ethinyl estradiol (0.1 to 2 times the normal human exposure) found an increase in carcinomas of the harderian gland in the group that received the high dose of drospirenone alone. A similar study in rats given 10 mg per kg per day drospirenone alone or 0.3 + 0.003, 3 + 0.03 and 10 + 0.1 mg per kg per day drospirenone and ethinyl estradiol (0.8 to 10 times the normal human exposure) found an increased incidence of benign and total adrenal gland pheochromocytomas in the group receiving the high dose of drospirenone.^{01}

Mutagenicity

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.^{01}

Pregnancy/Reproduction

Pregnancy—
Drospirenone and ethinyl estradiol is not recommended for use during pregnancy and should be discontinued immediately if pregnancy is suspected. Studies in animals that it causes serious adverse effects on the fetus^{01}

Of the 14 pregnancies that occurred with drospirenone and ethinyl estradiol exposure in utero, one produced an infant with esophageal atresia. Animal studies have revealed various teratogenic effects. A study in pregnant rats given oral drospirenone doses of 5, 15, and 45 mg per kg per day (6 to 50 times the normal human exposure) resulted in fetuses with delayed ossification. A study in rabbits found an increase in fetal loss and retardation of fetal development following oral drospirenone doses of 1, 30, and 100 mg per kg per day (2 to 27 times the human exposure. An increase in feminization of male rat fetuses was seen when drospirenone and ethinyl estradiol was administered during late pregnancy at doses of 5, 15, and 45 mg per kg. ^{01}

FDA Pregnancy Category X^{01}

Breast-feeding

Drospirenone and ethinyl estradiol is distributed into human breast milk and may cause adverse effects, jaundice and breast enlargement, on the child. The nursing mother should be advised not to use drospirenone and ethinyl estradiol until she has completely weaned her child.^{01}

Pediatrics

Use of drospirenone and ethinyl estradiol is not indicated in children that have not reached menarche.^{01}


Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):


Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.

Aldosterone antagonists or
» Angiotensin-converting enzyme (ACE) inhibitors or
Angiotensin-II receptor antagonists or
Anti-inflammatory drugs, nonsteroidal (NSAIDs) or
Diuretics, potassium-sparing or
Heparin    (concurrent use of these medications may increase serum potassium levels due to the antimineralocorticoid activity of drospirenone. Women receiving daily, long-term treatment for chronic conditions with these medications should have their serum potassium levels checked during the first treatment cycle )

^{01}
Acetaminophen    (oral contraceptives may induce the conjugation of acetaminophen, resulting in decreased plasma concentrations of acetaminophen)

^{01}    (concurrent use of acetaminophen with oral contraceptives may result in increased plasma concentrations of some synthetic estrogens, possibly by inhibition of conjugation^{01})


Ascorbic acid    (concurrent use of ascorbic acid with oral contraceptives may result in increased plasma concentrations of some synthetic estrogens, possibly by inhibition of conjugation)

^{01}
Atorvastatin    (coadministration with ethinyl estradiol resulted in an increased ethinyl estradiol AUC of 20%)

^{01}
Ampicillin or
» Griseofulvin or
Tetracycline     (there have been rare case reports of reduced oral contraceptive effectiveness in women taking ampicillin, griseofulvin, or tetracycline, resulting in unplanned pregnancy. Although the association is very weak, patients, especially long-term users of antibiotic therapy, should be advised of this information and given the option of using an alternate or additional method of contraception while taking any of these antibiotics)

^{01}
Clofibric acid or
Morphine or
Salicylic acid or
Temazepam    (concurrent use of oral contraceptives may result in increased clearance of clofibric acid, morphine, salicylic acid and temazepam)

^{01}
» Cyclosporine or
Prednisolone or
» Theophylline    (concurrent use of these medications with combined oral contraceptives containing ethinyl estradiol may inhibit the metabolism of these medications, which results in increased plasma concentrations of cyclosporine, prednisone, and theophylline )

^{01}
» Carbamazepine or
» Phenobarbital or
Phenylbutazone or
» Phenytoin or
» Rifampin or
St John's Wort     (concurrent use of these medications with oral contraceptives may increase ethinyl estradiol and some progestins metabolism, which could result in reduced contraceptive reliability and increased menstrual irregularities)

^{01}
» Smoking, tobacco    (oral contraceptives are not recommended with heavy tobacco use because of an increased risk of serious cardiovascular side effects. Risk increases with increased tobacco usage and with age, especially in women over 35 years of age)

^{01}

Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

With diagnostic test results
Glucose tolerance test, oral    (glucose tolerance may be decreased, resulting in higher 2 hour oral glucose tolerance test results)

^{01}
Thyroid function tests:
Thyroxine (T ₄) determinations    (estrogen-induced thyroid-binding globulin elevates the amount of T ₄ that is protein bound )

^{01}
Triiodothyronine (T ₃) determinations     ( T ₃ resin uptake is decreased because estrogens increase serum thyroid-binding globulin [TBG])

^{01}With physiology/laboratory test values
Androstenedione or
Ceruloplasmin, serum or
Dehydroepiandrosterone sulfate (DHEA-S) or
Pregnenolone or
Sex hormone–binding globulin (SHBG), serum or
Testosterone or
Thyroid-binding globulin or
Transferrin or cortisol-binding globulin, serum    (oral contraceptives increase protein synthesis of SHBG, thyroid-binding globulin, transferrin, and ceruloplasmin. The serum concentrations of total sex steroidsand corticoids may also increase. The free thyroid concentration is unchanged, and thyroid function is unaltered. Response of the free non–protein-bound component may be variable)

^{01}
Apolipoprotein A ₁, A ₂, or B or
Cholesterol, total or
Triglycerides    (in general, the net effect on lipoproteins is the result of the opposing actions of the estrogen and progestin and depends on the ratio between the two hormones. The estrogen component increases triglyceride, very low density lipoproteins (VLDL), and total cholesterol concentrations and decreases low density lipoproteins (LDL). The progestin component, if androgenic, decreases high density lipoproteins (HDL) and increases LDL. The low concentrations of the androgenic progestins in oral contraceptives have slight effect, which is of clinical significance only for some predisposed individuals. Sometimes, older women with higher serum concentrations of cholesterol may experience a reduction caused by a lowering of the serum LDL concentrations. Triglycerides are increased by all oral contraceptives because of the predominant estrogen effects. The increase in total cholesterol caused by desogestrel- and norgestimate-containing oral contraceptives is considered favorable because it is the net result of the increase in HDL ₃-C (an estrogen effect) without an increase in HDL ₂-C concentrations. The increase in HDL ₂-C caused by other low-dose oral contraceptives is considered an androgenic effect of some of the 19–nortestosterone-derived progestins)

^{01}
Clotting factors VII, VIII, IX, and X or
Prothrombin time or
Norepinephrine-induced platelet aggregability    (oral contraceptives increase levels of prothrombin, clotting factors VII,VIII, IX and X and norepinephrine-induced platelet aggregability)

^{01}
Folate, serum    (serum folate levels may be decreased with oral contraceptive therapy)

^{01}
Glucose, plasma or serum or
Insulin    (glucose intolerance has been reported in a significant percentage of oral contraceptives users. Progestogens increase insulin secretion and create insulin resistance; hyperinsulinism can occur in women using oral contraceptives containing greater than 75 micrograms of estrogens. Although fasting blood glucose is not affected in the nondiabetic woman, prediabetic and diabetic women should be carefully monitored while taking oral contraceptives)

^{01}
High density lipoproteins (HDL), serum    (low-dose oral contraceptives show no change or a decrease in value of HDL; the estrogen component increases HDL and the progestin component, if androgenic, lowers HDL )

^{01}
Low density lipoproteins (LDL), serum    (some progestins may elevate LDL levels and render control of hyperlipidemias more difficult)

^{01}
Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Except under special circumstances, this medication should not be used when the following medical problem exists:
Adrenal insufficiency or
Hepatic function impairment or
Renal insufficiency    (drospirenone and ethinyl estradiol should not be used in patients with conditions that predispose to hyperkalemia^{01})


» Carcinoma, breast, known or suspected or
» Carcinoma, endometrium or
» Neoplasia, estrogen-dependent, known or suspected    (may worsen conditions; estrogen-containing oral contraceptives should be discontinued and nonhormonal contraceptives initiated, although sometimes progestin-only contraceptives are used for selected patients)

^{01}
» Cardiac insufficiency    (oral contraceptives should not be used in patients with marginal cardiac reserve; fluid retention sometimes caused by estrogens may aggravate this condition)

^{01}
» Cerebrovascular disease, active or history of or
» Coronary artery disease, active or history of    (the estrogen component of oral contraceptives has a protective effect against atherosclerosis. Any association with risk in these conditions has been related to thrombosis or interference with cholesterol-lipoprotein profile. Oral contraceptives should be discontinued or strictly avoided if any cardiovascular or cerebrovascular accidents occur; users should switch to nonhormonal contraception. If oral contraceptives are used in women at risk, special monitoring may be required )

^{01}
Cholestatic jaundice of pregnancy or
Jaundice with prior pill use    (estrogens may increase risk of recurrence^{01})


» Hepatic disease, cholestatic, active or
» Hepatic tumors, benign or malignant, or history of    (metabolism of estrogens may be impaired; also, estrogens may worsen the condition. Oral contraceptives should be discontinued and nonhormonal contraception initiated; for those women with active hepatic disease, oral contraceptive use may be resumed after liver function tests return to normal)

^{01}
Pregnancy    (although studies have shown no increased risk of birth defects in women who have used oral contraceptives prior to pregnancy, and studies do not suggest a teratogenic effect of oral contraceptives when taken inadvertently during early pregnancy, oral contraceptives should be discontinued if pregnancy is confirmed and should not be used during pregnancy to treat threatened or habitual abortion or to induce withdrawal bleeding as a test for pregnancy)

^{01}
» Thrombophlebitis, thrombosis, or thromboembolic disorders, active or history of    (oral contraceptives are not recommended for women with predisposing factors, especially those who smoke tobacco or who have an underlying abnormality of the coagulation system, that place them at special risk for thrombosis. Problems generally have not been associated with the low doses of hormones used for contraception for women not at risk for these conditions)

^{01}    (cases of retinal thrombosis have been reported in association with the use of oral contraceptives. Oral contraceptives should be discontinued in patients with unexplained partial or complete loss of visionl; onset of proptosis or diplopia; papilledema; or retinal vascular lesions)

^{01}    (oral contraceptives should be started no earlier than 4 to 6 weeks after deliery because the immediate postpartum period is associated with an increased risk of thromboembolism)

^{01}
» Uterine bleeding, abnormal or undiagnosed    (malignancy should be ruled out in cases of persistent or recurring abnormal uterine bleeding.)

^{01}
Risk-benefit should be considered when the following medical problems exist
Gallbladder disease, or history of, especially gallstones    (the overall risk is low and thought to be of minimal clinical importance; however, cautious use of oral contraceptives is recommended with known gallbladder disease)

^{01}
Hypertension    (oral contraceptives have been shown to raise blood pressure in some normotensive women considered to be at high risk [although these women cannot be easily identified] or further raise blood pressure in hypertensive women)

^{01}
» Hyperkalemia or
» Elevated serum potassium levels    (drospirenone posseses antimineralocorticoid activity, which can increase the potential for hyperkalemia in high-risk patients)

^{01}
Mental depression, or history of    (the oral contraceptive should be discontinued if significant depression occurs, especially in women with a history of depression)

^{01}
Migraine headaches    (since migraine headaches have been associated with an increased risk of stroke, discontinuation of oral contraceptives may be warranted if migraine headaches are recurring, persistent, or more severe with use of oral contraceptives, especially for those individuals predisposed to thrombosis)

^{01}
Surgery, major    (concurrent oral contraceptive usage increases the relative risk of postoperative thromboembolism by two- to four-fold in predisposed women, especially for smokers of tobacco or for those women with a history of thromboembolism. When possible or if appropriate, oral contraceptives should be discontinued at least 4 weeks before and for 2 weeks after a major elective surgery^{01})



Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):

Blood pressure determinations and
Hepatic function determinations and
Papanicolaou (Pap) test and
Physical examinations    (recommended as determined by physician. Special attention should be given to breast, liver, and pelvic area in the physical exam and patients should be encouraged to self-examine breasts monthly^{01})

    (special attention to rule out malignancy should be given to patients complaining of persistent or recurring uterine bleeding)

^{01}
Glucose, serum and
Lipid profile, serum and
Lipoprotein profile, serum    (routine assessment is needed only for women at special risk, including women 35 years of age or older, women who have personal or strong family histories of heart disease, diabetes mellitus, or hypertension, or whose personal history includes gestational diabetes mellitus, xanthomatosis or obesity)

^{01}




Side/Adverse Effects
The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for immediate medical attention
Incidence rare
    
Cerebral hemorrhage (fever ; sudden loss of consciousness )^{01}
    
gallbladder disease ^{01}
    
myocardial infarction (crushing chest pain ; unexplained shortness of breath)^{01}
    
pulmonary embolism (anxiety ; burning pain in lower abdomen ; chest pain; chills; convulsions ; coughing ; feeling of heat ; feeling of warmth in lips and tongue; headache ; nervousness ; numbness of the fingertips; pain in lower back,; pelvis, or stomach ; ringing in the ears)^{01}
    
thromboembolism or thrombosis (abdominal pain, sudden, severe, or continuing; coughing up blood; headache, severe or sudden; loss of coordination, sudden; pains in chest, groin, or leg, especially calf of leg; shortness of breath, sudden, unexplained; slurring of speech, sudden; vision changes, sudden; weakness, numbness, or pain in arm or leg, unexplained)—mainly exhibited in women having predisposing or pre-existing conditions, especially for those who smoke tobacco, but the event may be idiopathic^{01}
    
thrombophlebitis (bluish color ; changes in skin color; pain ; tenderness ; swelling of foot or leg)^{01}



Those indicating need for medical attention
Incidence more frequent, especially during the first 3 months of oral contraceptive use
    
Changes in the menstrual bleeding pattern or intermenstrual bleeding, such as amenorrhea (complete stoppage of menstrual bleeding over several months), breakthrough bleeding (vaginal bleeding between regular menstrual periods, which may require the use of a pad or a tampon), scanty menses (very light menstrual bleeding), or spotting ( light vaginal bleeding between regular menstrual periods)^{01}

Incidence less frequent
    
Headaches or migraines, worsening or increased frequency of ^{01}
    
hypertension, worsening or exacerbation ^{01}
    
vaginal candidiasis or vaginitis, sporadic or recurrent (vaginal discharge, thick, white, or curd-like, or vaginal itching or other irritation)^{01}

Incidence rare
    
Breast tumors (lumps in breast)—primarily in women having a predisposing or pre-existing condition ^{01}
    
hepatic focal nodular hyperplasia, hepatitis, or hepatocellular carcinoma (pains in stomach, side, or abdomen, or yellow eyes or skin)—primarily in women having a predisposing or pre-existing condition, especially those who smoke tobacco ^{01}
    
hepatic cell adenomas, benign (swelling, pain, or tenderness in upper abdominal area)^{01}
    
mental depression, slight worsening — in pre-existing conditions ^{01}



Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
    
Abdominal cramping or bloating ^{01}
    
acne —usually less frequent after the first 3 months of use ^{01}
    
breast pain, tenderness, or swelling ^{01}
    
change in cervical erosion and secretion ^{01}
    
change in corneal curvature ^{01}
    
cholestatic jaundice ^{01}
    
dizziness ^{01}
    
infertility after discontinuation ^{01}
    
intolerance to contact lenses ^{01}
    
sodium and fluid retention (swelling of ankles and feet)^{01}

Incidence less frequent
    
Gain or loss of body or facial hair ^{01}
    
libido changes (increase or decrease of interest in sexual intercourse)^{01}
    
melasma (brown, blotchy spots on exposed skin)^{01}
    
weight gain or loss ^{01}

Note: Melasma usually is temporary but can be permanent. Women having dark complexions, having a history of melasma during pregnancy, or having prolonged exposure to sunlight are most susceptible to developing melasma.^{01}






Overdose
Serious adverse effects generally do not occur with an acute overdosage. When children have accidently ingested a large amount of an oral contraceptive, more serious adverse effects also did not result. Withdrawal bleeding has occasionally occurred in young girls and does not require treatment. ^{01}

For more information on the management of overdose or unintentional ingestion, contact a poison control center (see Poison Control Center Listing).

Clinical effects of overdose
The following effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:
    
Nausea or vomiting^{01}


Treatment of overdose
Specific treatment—Nausea or vomiting is treated for symptomatic relief.^{01}

Supportive care—Patients in whom intentional overdose is known or suspected should be referred for psychiatric consultation.^{01}


Monitoring:
Serum concentrations of potassium and sodium, and evidence of metabolic acidosis, should be monitored^{01}



Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Drospirenone and Ethinyl Estradiol (Systemic).
In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Hypersensitivity to estrogens or progestins

Pregnancy—Not recommended for use during pregnancy





Breast-feeding—Oral contraceptives are distributed into breast milk



Use in adolescents—
Careful counseling may be required to increase compliance

Other medications, especially angiotensin-converting enzyme (ACE) inhibitors, carbamazapine, cyclosporine, griseofulvin, phenobarbital, phenytoin, rifampin, theophylline, or tobacco smoking
Other medical problems, especially carcinoma of the breast (known or suspected); carcinoma of the endometrium; cardiac insufficiency; cerebrovascular disease—especially if patient smokes cigarettes (active or history of); coronary artery disease; estrogen-dependent neoplasia (known or suspected); hepatic disease, cholestatic (active); hepatic tumors, benign or malignant (active or history of); hyperkalemia or elevated serum potassium levels; thrombophlebitis, thrombosis, or thromboembolic disorders (active or history of); or uterine bleeding (abnormal or undiagnosed)

Proper use of this medication
» Reading patient package insert carefully

Using an additional method of birth control for the first 7 days; some clinicians may recommend that an additional method of birth control be used during the first cycle of oral contraceptive use

» Compliance with therapy; taking medication at the same time each day, at 24-hour intervals

Keeping an extra 1-month supply available when possible

Taking tablets in proper (color-coded) sequence

» Proper dosing
Missing 1 yellow “active” tablet—Taking as soon as possible; taking the next tablet at the scheduled time even if it means taking two tablets in one day

Missing 2 yellow “active” tablets in a row in the first or second week—Taking two tablets on the day you remember and two tablets the following day; continuing on regular dosing schedule and using another birth control method for 7 days after the last missed dose

Missing 2 yellow “active” tablets in a row in the 3 week or

Missing 3 or more yellow “active” tablets in a row (during the first 3 weeks)—

• Using Day-1 start: Starting a new cycle on the day you remember; discarding remaining doses for current cycle and using a second method of birth control, additionally, for 7 days after the last missed dose; contacting health care professional if two menstrual periods are missed


• Using Sunday start: Continuing on regular dosing schedule for current cycle until Sunday; on Sunday, throwing out remaining doses for current cycle and beginning a new cycle; using an additional method of birth control for 7 days after the last missed dose; contacting health care professional if two menstrual periods are missed


Missing any of the last 7 white tablets is not important, but beginning new cycle on time is essential

Proper storage

Precautions while using this medication
» Regular visits to physician at least every 6 to 12 months to check progress

What to expect and do if vaginal bleeding occurs

What to expect and do if a menstrual period is missed; contacting health professional if two menstrual periods are missed

» Stopping medication immediately and checking with physician if pregnancy is suspected

If scheduled for laboratory tests, telling physician if taking birth control pills; certain blood tests may be affected by oral contraceptives

Not refilling an old prescription for oral contraceptives without having a physical examination by physician, especially after a pregnancy


Side/adverse effects
Signs of potential side effects, especially cerebral hemorrhage; gallbladder disease; myocardial infarction; pulmonary embolism; thromboembolism or thrombosis; thrombophlebitis; changes in the menstrual bleeding pattern or intermenstrual bleeding; headaches or migraines; hypertension, worsening; vaginal candidiasis or vaginitis; breast tumors (usually for predisposed individuals); hepatic focal nodular hyperplasia, hepatitis, or hepatocellular carcinoma; hepatic cell adenomas, benign; slight worsening of mental depression

Cigarette smoking combined with oral contraceptive use causes increased risk of serious thromboembolic or hepatic side effects, especially for heavy smokers or women over age 35


For oral dosing forms:
Maximum contraceptive effect is obtained by taking doses at 24-hour intervals and beginning the new regimen on time. It is recommended to take drospirenone and ethinyl estradiol combination oral contraceptive at the same time each day, preferably after the evening meal or at bedtime.^{01}

To begin taking drospirenone and ethinyl estradiol combination oral contraceptive, the first tablet is taken either on Day 1 (first day of menstrual bleeding) of the menstrual cycle or the first Sunday following the start of menses. The treatment regimen consists of 21 tablets of a monophasic combined drospirenone and ethinyl estradiol in yellow color and 7 inert (nonhormonal) tablets in white color.^{01}

The patient should be advised to begin her next and all subsequent 28-day treatment cycles of drospirenone and ethinyl estradiol combination oral contraceptive on the same day of the week that she began her first treatment cycle, following the same schedule. A periodic pill-free rest period is not recommended. Patients should be informed to take their 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.^{01}

Treatment with drospirenone and ethinyl estradiol combination oral contraceptive may be initiated 4 weeks postpartum in the nonlactating mother; the increased risk of thromboembolic disease associated with the postpartum period must be considered. The use of drospirenone and ethinyl estradiol combination oral contraceptive is not recommended in the nursing mother until she has completely weaned her child.^{01}


Oral Dosage Forms

DROSPIRENONE AND ETHINYL ESTRADIOL TABLETS

Usual Adult and Adolescent Dose
Contraceptive, systemic
Oral, 1 yellow active tablet a day for twenty-one consecutive days commencing on Day 1 of the menstrual cycle or on the first Sunday after the menstrual cycle begins followed by 1 white inert tablet a day on menstrual cycle days 22 through 28. The next round of treatment is begun on the eighth day after the last tablet of the previous cycle has been taken. Tablets should be taken at the same time each day, preferably after the evening meal or at bedtime.^{01}


Note: With a Sunday start schedule, the patient should take her first tablet on the first Sunday after the onset of menstruation. If the patients period begins on a Sunday, she should take her first tablet that same day.^{01}
With a Day-1 start schedule, the patient should take her first tablet on Day 1 of the menstrual cycle.^{01}
The last seven tablets of the twenty-eight day cycle contain no hormones. These seven companion tablets are a different color, white, from those containing hormones.^{01}


Strength(s) usually available
U.S.—


3 mg of drospirenone and 0.03 mg of ethinyl estradiol (Rx) [Yasmin (corn starch NF) ( ferric oxide pigment) (hydroxylpropylmethyl cellulose USP) (lactose monohydrate NF) ( macrogol 6000 NF) (magnesium stearate NF) (modified starch NF) (povidone 25000 USP) (talc USP) (titanium dioxide USP) (yellow NF)]^{01}

Note: Available in twenty-eight–day cycle which includes seven days of placebo tablets.


Packaging and storage:
Store at 25 °C (77 °F); excursions permitted to 15-30° C (59-86° F) in a tight container. ^{01}

Auxiliary labeling:
   • Avoid cigarettes.^{01}
   • Avoid too much sun or use of sunlamp.^{01}

Note: Include mandatory patient package inserts (PPIs) (the brief summary of patient labeling and the detailed patient labeling) when dispensing.^{01}

Developed: 07/25/2001

References

1. Product Information: Yasmin (R), drospirenone and ethinyl estradiol. Berlex Laboratories, Wayne, New Jersey, (PI revised 5/2001) reviewed 6/2001.