YAZ is indicated for the prevention of pregnancy in women who elect to use an oral contraceptive.

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

YAZ is also indicated for the treatment of symptoms of premenstrual dysphoric disorder (PMDD) in women who choose to use an oral contraceptive as their method of contraception. The effectiveness of YAZ for PMDD when used for more than three menstrual cycles has not been evaluated.

The essential features of PMDD according to the Diagnostic and Statistical Manual-4th edition (DSM-IV) include markedly depressed mood, anxiety or tension, affective lability, and persistent anger or irritability. Other features include decreased interest in usual activities, difficulty concentrating, lack of energy, change in appetite or sleep, and feeling out of control. Physical symptoms associated with PMDD include breast tenderness, headache, joint and muscle pain, bloating and weight gain. In this disorder, these symptoms occur regularly during the luteal phase and remit within a few days following onset of menses; the disturbance markedly interferes with work or school, or with usual social activities and relationships with others. Diagnosis is made by healthcare providers according to DSM-IV criteria, with symptomatology assessed prospectively over at least two menstrual cycles. In making the diagnosis, care should be taken to rule out other cyclical mood disorders. YAZ has not been evaluated for the treatment of premenstrual syndrome (PMS).

YAZ is indicated for the treatment of moderate acne vulgaris in women at least 14 years of age, who have no known contraindications to oral contraceptive therapy and have achieved menar-che. YAZ should be used for the treatment of acne only if the patient desires an oral contraceptive for birth control.

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

Oral Contraceptive Clinical Trial

In the primary contraceptive efficacy study of YAZ (3 mg DRSP/ 0.02 mg EE) of up to 1 year duration, 1,027 subjects were enrolled and completed 11,480 28-day cycles of use. The age range was 17 to 36 years. The racial demographic was: 87.8% Caucasian, 4.6% Hispanic, 4.3% Black, 1.2% Asian, and 2.1% other. Women with a BMI greater than 35 were excluded from the trial. The pregnancy rate (Pearl Index) was 1.41 per 100 woman-years of use based on 12 pregnancies that occurred after the onset of treatment and within 14 days after the last dose of YAZ in women 35 years of age or younger during cycles in which no other form of contraception was used.

Premenstrual Dysphoric Disorder Clinical Trials

Two multicenter, double-blind, randomized, placebo-controlled studies were conducted to evaluate the effectiveness of YAZ in treating the symptoms of PMDD. Women aged 18-42 who met DSM-IV criteria for PMDD, confirmed by prospective daily ratings of their symptoms, were enrolled. Both studies measured the treatment effect of YAZ using the Daily Record of Severity of Problems scale, a patient-rated instrument that assesses the symptoms that constitute the DSM-IV diagnostic criteria. The primary study was a parallel group design that included 384 evaluable reproductive-aged women with PMDD who were randomly assigned to receive YAZ or placebo treatment for 3 menstrual cycles. The supportive study, a crossover design, was terminated prematurely prior to achieving recruitment goals due to enrollment difficulties. A total of 64 women of reproductive age with PMDD were treated initially with YAZ or placebo for up to 3 cycles followed by a washout cycle and then crossed over to the alternate medication for 3 cycles.

Efficacy was assessed in both studies by the change from baseline during treatment using a scoring system based on the first 21 items of the Daily Record of Severity of Problems. Each of the 21 items was rated on a scale from 1 (not at all) to 6 (extreme); thus a maximum score of 126 was possible. In both trials, women who received YAZ had statistically significantly greater improvement in their Daily Record of Severity of Problems scores. In the primary study, the aver-age decrease (improvement) from baseline was 37.5 points in women taking YAZ, compared to 30.0 points in women taking placebo.

Acne Clinical Trials

In two multicenter, double blind, randomized, placebo-controlled studies, 889 subjects, ages 14 to 45 years, with moderate acne received YAZ or placebo for six 28 day cycles. The primary efficacy endpoints were the percent change in inflammatory lesions, non-inflammatory lesions, total lesions, and the percentage of subjects with a “clear” or “almost clear” rating on the Investigator's Static Global Assessment (ISGA) scale on day 15 of cycle 6, as presented in Table III:

Table III: Efficacy Results for Acne Trials*

Oral Contraception and PMDD

To achieve maximum contraceptive and PMDD effectiveness, YAZ (drospirenone and ethinyl estradiol) must be taken exactly as directed at intervals not exceeding 24 hours.

YAZ consists of 24 light pink active tablets of a monophasic combined hormonal preparation plus 4 inert white tablets. The dosage of YAZ is one light pink tablet daily for 24 consecutive days followed by 4 white inert tablets per menstrual cycle. A patient should begin to take YAZ either on the first day of her menstrual period (Day 1 Start) or on the first Sunday after the onset of her menstrual period (Sunday Start).

Day 1 Start. During the first cycle of YAZ use, the patient should be instructed to take one light pink YAZ daily, beginning on Day one (1) of her menstrual cycle. (The first day of menstruation is Day one.) She should take one light pink YAZ daily for 24 consecutive days, followed by one white inert tablet daily on menstrual cycle days 25 through 28. It is recommended that YAZ be taken at the same time each day, preferably after the evening meal or at bedtime. YAZ can be taken without regard to meals. If YAZ is first taken later than the first day of the menstrual cycle, YAZ should not be considered effective as a contraceptive until after the first 7 consecutive days of product administration. The possibility of ovulation and conception prior to initiation of medication should be considered.

Sunday Start. During the first cycle of YAZ use, the patient should be instructed to take one light pink YAZ daily, beginning on the first Sunday after the onset of her menstrual period. She should take one light pink YAZ daily for 24 consecutive days, followed by one white inert tablet daily on menstrual cycle days 25 through 28. It is recommended that YAZ be taken at the same time each day, preferably after the evening meal or at bedtime. YAZ can be taken without regard to meals. YAZ should not be considered effective as a contraceptive until after the first 7 consecutive days of product administration. The possibility of ovulation and conception prior to initiation of medication should be considered.

The patient should begin her next and all subsequent 28-day regimens of YAZ on the same day of the week that she began her first regimen, following the same schedule. She should begin taking her light pink tablets on the next day after ingestion of the last white tablet, regardless of whether or not a menstrual period has occurred or is still in progress. Anytime a subsequent cycle of YAZ is started later than the day following administration of the last white tablet, the patient should use another method of contraception until she has taken a light pink YAZ daily for seven consecutive days.

When switching from another oral contraceptive, YAZ should be started on the same day that a new pack of the previous oral contraceptive would have been started.

Withdrawal bleeding usually occurs within 3 days following the last light pink tablet. If spotting or breakthrough bleeding occurs while taking YAZ, the patient should be instructed to continue taking her YAZ as instructed and by the regimen described above. She should be instructed that this type of bleeding is usually transient and without significance; however, if the bleeding is persistent or pro-longed, the patient should be advised to consult her physician.

Although the occurrence of pregnancy is low if YAZ is taken according to directions, if withdrawal bleeding does not occur, the possibility of pregnancy must be considered. If the patient has not adhered to the prescribed dosing schedule (missed one or more active tablets or started taking them on a day later than she should have), the possibility of pregnancy should be considered at the time of the first missed period and appropriate diagnostic measures taken. If the patient has adhered to the pre-scribed regimen and misses two consecutive periods, pregnancy should be ruled out. Hormonal contraceptives should be discontinued if pregnancy is confirmed.

The risk of pregnancy increases with each active light pink tablet missed. For additional patient instructions regarding missed pills, see the "WHAT TO DO IF YOU MISS PILLS" section in the DETAILED PATIENT LABELING which follows. If breakthrough bleeding occurs following missed tablets, it will usually be transient and of no consequence. If the patient misses one or more white tablets, she should still be protected against pregnancy provided she begins taking light pink tablets again on the proper day.

In the nonlactating mother, YAZ may be initiated 4-6 weeks postpartum, for contraception. When the tablets are administered in the postpartum period, the increased risk of thromboembolic disease associated with the postpartum period must be considered. (See CONTRAINDICATIONS, WARNINGS, and PRECAUTIONS concerning thromboembolic disease.)

Acne

The timing and initiation of dosing with YAZ in women with acne should follow the guideline for use of YAZ as an oral contraceptive. The 28-day dosage regimen for YAZ for treating facial acne consists of one active tablet daily for 24 consecutive days followed by one inert tablet daily for 4 days. After 28 tablets are taken, a new course is started the next day.

YAZ (drospirenone and ethinyl estradiol) Tablets are available in packages of 3 BLISTER packs (NDC 50419-405-03). Each pack contains 24 active light pink round, unscored, film-coated tablets debossed with a “DS” in a regular hexagon on one side, each containing 3 mg drospirenone and 0.02 mg ethinyl estradiol, and 4 inert white round, unscored, film-coated tablets debossed with a “DP” in a regular hexagon on one side.

Store at 25° C (77° F); excursions permitted to 15–30° C (59–86° F) [See USP Controlled Room Temperature].

REFERENCES FURNISHED UPON REQUEST

Manufactured for:
Bayer HealthCare Pharmaceuticals
Bayer HealthCare Pharmaceuticals Inc. Wayne, NJ 07470

Manufactured in Germany
©2007, Bayer HealthCare Pharmaceuticals Inc. All Rights Reserved.

February 2007
FDA rev date: 1/26/2007

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