Safyral

SAFYRAL- drospirenone/ethinyl estradiol/levomefolate calcium and levomefolate calcium
Bayer HealthCare Pharmaceuticals Inc.

1 INDICATIONS AND USAGE

1.1 Oral Contraceptive

Safyral is indicated for use by women to prevent pregnancy.

1.2 Folate Supplementation

Safyral is indicated in women who choose to use an oral contraceptive as their method of contraception, to raise folate levels for the purpose of reducing the risk of a neural tube defect in a pregnancy conceived while taking the product or shortly after discontinuing the product.

2 DOSAGE AND ADMINISTRATION

2.1 How to Take Safyral

Take one tablet by mouth at the same time every day. The failure rate may increase when pills are missed or taken incorrectly.

To achieve maximum contraceptive effectiveness, Safyral must be taken as directed, in the order directed on the blister pack. Single missed pills should be taken as soon as remembered.

2.2 How to Start Safyral

Instruct the patient to begin taking Safyral 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 Safyral use, instruct the patient to take one orange Safyral daily, beginning on Day 1 of her menstrual cycle. (The first day of menstruation is Day 1.) She should take one orange Safyral daily for 21 consecutive days, followed by one light orange tablet, containing levomefolate alone, daily on Days 22 through 28. Safyral should be taken in the order directed on the package at the same time each day, preferably after the evening meal or at bedtime with some liquid, as needed. Safyral can be taken without regard to meals. If Safyral is first taken later than the first day of the menstrual cycle, Safyral should not be considered effective as a contraceptive until after the first 7 consecutive days of product administration. Instruct the patient to use a non-hormonal contraceptive as back-up during the first 7 days. The possibility of ovulation and conception prior to initiation of medication should be considered.

Sunday Start

During the first cycle of Safyral use, instruct the patient to take one orange Safyral daily, beginning on the first Sunday after the onset of her menstrual period. She should take one orange Safyral daily for 21 consecutive days, followed by one light orange tablet, containing levomefolate alone, daily on Days 22 through 28. Safyral should be taken in the order directed on the package at the same time each day, preferably after the evening meal or at bedtime with some liquid, as needed. Safyral can be taken without regard to meals. Safyral should not be considered effective as a contraceptive until after the first 7 consecutive days of product administration. Instruct the patient to use a non-hormonal contraceptive as back-up during the first 7 days. 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 Safyral on the same day of the week that she began her first regimen, following the same schedule. She should begin taking her orange tablets on the next day after ingestion of the last light orange folate tablet, regardless of whether or not a menstrual period has occurred or is still in progress. Anytime a subsequent cycle of Safyral is started later than the day following administration of the last light orange tablet, the patient should use another method of contraception until she has taken an orange Safyral daily for seven consecutive days.

When switching from a different birth control pill

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

When switching from a method other than a birth control pill

When switching from a transdermal patch or vaginal ring, Safyral should be started when the next application would have been due. When switching from an injection, Safyral should be started when the next dose would have been due. When switching from an intrauterine contraceptive or an implant, Safyral should be started on the day of removal.

Withdrawal bleeding usually occurs within 3 days following the last orange tablet. If spotting or breakthrough bleeding occurs while taking Safyral, instruct the patient to continue taking Safyral by the regimen described above. Counsel her that this type of bleeding is usually transient and without significance; however, advise her that if the bleeding is persistent or prolonged, she should consult her healthcare provider.

Although the occurrence of pregnancy is low if Safyral is taken according to directions, if withdrawal bleeding does not occur, consider the possibility of pregnancy. 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), consider the possibility of pregnancy at the time of the first missed period and take appropriate diagnostic measures. If the patient has adhered to the prescribed regimen and misses two consecutive periods, rule out pregnancy. Discontinue Safyral if pregnancy is confirmed.

The risk of pregnancy increases with each active orange tablet missed. For additional patient instructions regarding missed pills, see the “WHAT TO DO IF YOU MISS PILLS” section in the FDA-Approved Patient Labeling. If breakthrough bleeding occurs following missed tablets, it will usually be transient and of no consequence. If the patient misses one or more light orange tablets, she should still be protected against pregnancy provided she begins taking a new cycle of orange tablets on the proper day.

For postpartum women who do not breastfeed or after a second trimester abortion, start Safyral no earlier than 4 weeks postpartum due to the increased risk of thromboembolism. If the patient starts Safyral postpartum and has not yet had a period, evaluate for possible pregnancy, and instruct her to use an additional method of contraception until she has taken Safyral for 7 consecutive days.

2.3 Advice in Case of Gastrointestinal Disturbances

In case of severe vomiting or diarrhea, absorption may not be complete and additional contraceptive measures should be taken. If vomiting occurs within 3-4 hours after tablet-taking, this can be regarded as a missed tablet.

2.4 Folate Supplementation

The U.S. Preventive Services Task Force recommends that women of childbearing age consume supplemental folic acid in a dose of at least 0.4 mg (400 mcg) daily.¹ Consider other folate supplementation that a woman may be taking before prescribing Safyral. Ensure that folate supplementation is maintained if a woman discontinues Safyral due to pregnancy.

3 DOSAGE FORMS AND STRENGTHS

Safyral (drospirenone/ethinyl estradiol/levomefolate calcium tablets and levomefolate calcium tablets) is available in blister packs.

Each blister pack contains 28 film-coated, round, bi-convex tablets in the following order:

•

21 orange tablets each containing 3 mg drospirenone (DRSP), 0.03 mg ethinyl estradiol (EE) as betadex clathrate and 0.451 mg levomefolate calcium embossed with a “Y+” in a regular hexagon on one side

•

7 light orange tablets each containing 0.451 mg levomefolate calcium embossed with a “M+” in a regular hexagon on one side

4 CONTRAINDICATIONS

Safyral is contraindicated in females who are known to have or develop the following conditions:

•

Renal impairment

•

Adrenal insufficiency

•

A high risk of arterial or venous thrombotic diseases. Examples include women who are known to:

•

Smoke, if over age 35 [see Boxed Warning and Warnings and Precautions (5.1)]

•

Have deep vein thrombosis or pulmonary embolism, now or in the past [see Warnings and Precautions (5.1) ]

•

Have cerebrovascular disease [see Warnings and Precautions (5.1)]

•

Have coronary artery disease [see Warnings and Precautions (5.1)]

•

Have thrombogenic valvular or thrombogenic rhythm diseases of the heart (for example, subacute bacterial endocarditis with valvular disease, or atrial fibrillation) [see Warnings and Precautions (5.1)]

•

Have inherited or acquired hypercoagulopathies [see Warnings and Precautions (5.1)]

•

Have uncontrolled hypertension [see Warnings and Precautions (5.6)]

•

Have diabetes mellitus with vascular disease [see Warnings and Precautions (5.8)]

•

Have headaches with focal neurological symptoms or have migraine headaches with or without aura if over age 35 [see Warnings and Precautions (5.9)]

•

Undiagnosed abnormal uterine bleeding [see Warnings and Precautions (5.10)]

•

Current diagnosis of, or history of, breast cancer, which may be hormone-sensitive [see Warnings and Precautions (5.3)]

•

Liver tumor (benign or malignant) or liver disease [see Warnings and Precautions (5.4) and Use in Specific Populations (8.7)]

•

Pregnancy, because there is no reason to use COCs during pregnancy [see Warnings and Precautions (5.11) and Use in Specific Populations (8.1)]

•

Use of Hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir due to the potential for ALT elevations [see Warnings and Precautions (5.5) and Drug Interactions (7.3)].