Aviane

Aviane (levonorgestrel and ethinyl estradiol tablets) is indicated for use by females of reproductive potential to prevent pregnancy.

Limitations of use: The efficacy of Aviane (levonorgestrel and ethinyl estradiol tablets) in women with a body mass index (BMI) of > 35 kg/m2 has not been adequately evaluated.

In a clinical trial with Aviane (levonorgestrel and ethinyl estradiol tablets), 1,477 subjects had 7,720 cycles of use and a total of 5 pregnancies were reported. This represents an overall pregnancy rate of 0.84 per 100 woman-years. This rate includes patients who did not take the drug correctly. One or more pills were missed during 1,479 (18.8%) of the 7,870 cycles; thus all tablets were taken during 6,391 (81.2%) of the 7,870 cycles. Of the total 7,870 cycles, a total of 150 cycles were excluded from the calculation of the Pearl index due to the use of backup contraception and/or missing 3 or more consecutive pills.

The mean BMI of the study population was 24 kg/m2. Females with a BMI greater than 30 kg/m2 accounted for 12.1% (n=179) of the study population. Females with a BMI over 35 kg/m2 accounted for 4.3% (n=63) of the study population.

To achieve maximum contraceptive effectiveness, Aviane (levonorgestrel and ethinyl estradiol tablets) must be taken exactly as directed and at intervals not exceeding 24 hours. The dosage of Aviane-28 is one orange tablet daily for 21 consecutive days, followed by one light-green inert tablet daily for 7 consecutive days, according to the prescribed schedule. It is recommended that Aviane-28 tablets be taken at the same time each day.

The dispenser should be kept in the wallet supplied to avoid possible fading of the pills. If the pills fade, patients should continue to take them as directed.

During the first cycle of use

The possibility of ovulation and conception prior to initiation of medication should be considered. The patient should be instructed to begin taking Aviane on either the first Sunday after the onset of menstruation (Sunday Start) or on Day 1 of menstruation (Day 1 Start).

Sunday start:

The patient is instructed to begin taking Aviane-28 on the first Sunday after the onset of menstruation. If menstruation begins on a Sunday, the first tablet (orange) is taken that day. One orange tablet should be taken daily for 21 consecutive days, followed by one light-green inert tablet daily for 7 consecutive days. Withdrawal bleeding should usually occur within 3 days following discontinuation of orange tablets and may not have finished before the next pack is started. During the first cycle, contraceptive reliance should not be placed on Aviane-28 until an orange tablet has been taken daily for 7 consecutive days, and a nonhormonal back-up method of birth control should be used during those 7 days.

Day 1 start:

During the first cycle of medication, the patient is instructed to begin taking Aviane-28 during the first 24 hours of her period (day one of her menstrual cycle). One orange tablet should be taken daily for 21 consecutive days, followed by one light-green inert tablet daily for 7 consecutive days. Withdrawal bleeding should usually occur within 3 days following discontinuation of orange tablets and may not have finished before the next pack is started. If medication is begun on day one of the menstrual cycle, no back-up contraception is necessary. If Aviane-28 tablets are started later than day one of the first menstrual cycle or postpartum, contraceptive reliance should not be placed on Aviane-28 tablets until after the first 7 consecutive days of administration, and a nonhormonal back-up method of birth control should be used during those 7 days.

After the first cycle of use

The patient begins her next and all subsequent courses of tablets on the day after taking her last light-green tablet. She should follow the same dosing schedule: 21 days on orange tablets followed by 7 days on light-green tablets. If in any cycle the patient starts tablets later than the proper day, she should protect herself against pregnancy by using a nonhormonal back-up method of birth control until she has taken an orange tablet daily for 7 consecutive days.

Switching from another hormonal method of contraception

When the patient is switching from a 21-day regimen of tablets, she should wait 7 days after her last tablet before she starts Aviane. She will probably experience withdrawal bleeding during that week. She should be sure that no more than 7 days pass after her previous 21-day regimen. When the patient is switching from a 28-day regimen of tablets, she should start her first pack of Aviane on the day after her last tablet. She should not wait any days between packs. The patient may switch any day from a progestin-only pill and should begin Aviane the next day. If switching from an implant or injection, the patient should start Aviane on the day of implant removal or, if using an injection, the day the next injection would be due. In switching from a progestin-only pill, injection, implant, or intrauterine system (IUS), the patient should be advised to use additional nonhormonal contraception (such as condoms) until active tablets have been taken for 7 consecutive days of the first pack.

If spotting or breakthrough bleeding occurs

If spotting or breakthrough bleeding occur, the patient is instructed to continue on the same regimen. This type of bleeding is usually transient and without significance; however, if the bleeding is persistent or prolonged, the patient is advised to consult her physician.

Risk of pregnancy if tablets are missed

While there is little likelihood of ovulation occurring if only one or two orange tablets are missed, the possibility of ovulation increases with each successive day that scheduled orange tablets are missed. Although the occurrence of pregnancy is unlikely if Aviane 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 schedule (missed one or more tablets or started taking them on a day later than she should have), the probability of pregnancy should be considered at the time of the first missed period and appropriate diagnostic measures taken. If the patient has adhered to the prescribed regimen and misses two consecutive periods, pregnancy should be ruled out.

The risk of pregnancy increases with each active (orange) tablet missed. For additional patient instructions regarding missed tablets, see the WHAT TO DO IF YOU MISS PILLS section in the DETAILED PATIENT LABELING below.

Use after pregnancy, abortion or miscarriage

Aviane may be initiated no earlier than day 28 postpartum in the nonlactating mother or after a second trimester abortion due to the increased risk for thromboembolism (see  C ONTRAINDICATIONS, WARNINGS, and PRECAUTIONS concerning thromboembolic disease). The patient should be advised to use additional nonhormonal contraception (such as condoms) until active tablets have been taken for 7 consecutive days.

Aviane may be initiated immediately after a first trimester abortion or miscarriage. Instruct the patient to use additional nonhormonal contraception (such as condoms) until active tablets have been taken for 7 consecutive days, unless starting Aviane on the day of surgical abortion.

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

Thromboembolic and thrombotic disorders and other vascular problems (including thrombophlebitis and venous thrombosis with or without pulmonary embolism, mesenteric thrombosis, arterial thromboembolism, myocardial infarction, cerebral hemorrhage, cerebral thrombosis), carcinoma of the reproductive organs and breasts, hepatic neoplasia (including hepatic adenomas or benign liver tumors), ocular lesions (including retinal vascular thrombosis), gallbladder disease, carbohydrate and lipid effects, elevated blood pressure, and headache including migraine.

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).

Three studies compared breast cancer risk between current or recent COC users (<6 months since last use) and never users of COCs (Figure 2). 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.

The following adverse reactions associated with the use of oral CHCs were identified in clinical studies or postmarketing reports. Because some of these reactions were reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Common adverse reactions associated with oral CHCs are headache, abdominal pain, nausea, metrorrhagia, vaginal moniliasis and pain, acne, and vaginitis.

Additional adverse reactions that have been reported include the following:

Eye disorder: intolerance to contact lenses, steepening of corneal curvature

Gastrointestinal disorders: Abdominal bloating, vomiting

General disorders and administration site conditions: Edema, fluid retention

Hepatobiliary disorders: Cholestatic jaundice

Psychiatric disorders: Change in libido, mood changes

Reproductive system and breast disorders: Amenorrhea, breast tenderness, breast pain, breast enlargement, increased cervical mucous, change in menstrual flow, unscheduled bleeding

Skin and subcutaneous tissue disorders: Acne, melasma

Vascular disorders: Budd-Chiari syndrome, aggravation of varicose veins

To report SUSPECTED ADVERSE EVENTS, contact Teva at 1-888-838-2872 or FDA at 1-800-FDA-1088 or http://www.fda.gov/medwatch for voluntary reporting of adverse reactions.

21 orange active tablets each containing 0.10 mg of levonorgestrel, USP (-)-13-Ethyl-17-hydroxy-18,19-dinor-17α-pregn-4-en-20-yn-3-one, a totally synthetic progestogen, and 0.02 mg of ethinyl estradiol, USP, (19-Nor-17α-pregna-1,3,5(10)-trien-20-yne-3,17-diol). The inactive ingredients present are: FD&C yellow no. 6 aluminum lake, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, polyethylene glycol, pregelatinized corn starch, sodium starch glycolate and titanium dioxide.

7 light-green, inert tablets each containing: D&C yellow no. 10 aluminum lake, FD&C blue no. 1 aluminum lake, FD&C yellow no. 6 aluminum lake, lactose monohydrate, magnesium stearate, microcrystalline cellulose and pregelatinized corn starch.

Levonorgestrel, USP

C21H28O2 M.W. 312.45

Ethinyl Estradiol, USP

C20H24O2 M.W. 296.40