Drospirenone/Ethinyl Estradiol/Levomefolate Calcium Tablets and Levomefolate

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

Storage And Handling

Safyral (drospirenone/ethinyl estradiol/levomefolate calcium tablets and levomefolate calcium tablets) is available in packages of three blister packs (NDC 50419-403-03).

The film-coated tablets are rounded with biconvex faces, one side is embossed with a regular hexagon shape with Y+ or M+.

Each blister pack contains 28 film-coated tablets in the following order:

• 21 round, biconvex, orange, film-coated tablets with embossed “Y+” in a regular hexagon on one side each containing 3 mg drospirenone, 0.03 mg ethinyl estradiol, and 0.451 mg levomefolate calcium
• 7 round, biconvex, light orange, film-coated tablets with embossed “M+” in a regular hexagon on one side each containing 0.451 mg levomefolate calcium

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

REFERENCES

1. US Preventive Services Task Force. Folic Acid for the Prevention of Neural Tube Defects: US Preventive Services Task Force Recommendation Statement. Ann Intern Med 2009;150:626-631.

Distributed by: Bayer HealthCare Pharmaceuticals Inc. Revised: Aug 2017

Drospirenone and ethinyl estradiol prevent ovulation (the release of an egg from an ovary) and also cause changes in your cervical and uterine lining, making it harder for sperm to reach the uterus and harder for a fertilized egg to attach to the uterus. Levomefolate is a type of B vitamin that helps prevent a rare birth defect that could occur in a baby if the pregnancy occurs while taking birth control pills or shortly after stopping them.

Drospirenone, ethinyl estradiol, and levomefolate is used as contraception to prevent pregnancy. The Beyaz brand of this medication is also used to treat moderate acne in women who are at least 14 years old and have started having menstrual periods, and who wish to use birth control pills.

Beyaz is also used to treat the symptoms of premenstrual dysphoric disorder (PMDD), such as anxiety, depression, irritability, trouble concentrating, lack of energy, sleep or appetite changes, breast tenderness, joint or muscle pain, headache, and weight gain.

Drospirenone, ethinyl estradiol, and levomefolate may also be used for purposes not listed in this medication guide.

This medication can cause birth defects. Do not use if you are pregnant. Tell your doctor right away if you become pregnant, or if you miss two menstrual periods in a row. If you have recently had a baby, wait at least 4 weeks before taking birth control pills.

You should not take birth control pills if you have:

• untreated or uncontrolled high blood pressure, heart disease, or a history of heart attack, stroke, or blood clot;
• a blood-clotting disorder or circulation problems;
• problems with your eyes, kidneys or circulation caused by diabetes;
• a history of hormone-related cancer such as breast or uterine cancer;
• unusual vaginal bleeding that has not been checked by a doctor;
• severe migraine headaches, especially if you are older than 35;
• liver disease or liver cancer, a history of jaundice caused by pregnancy or birth control pills; or
• if you smoke and are over 35 years old.

To make sure you can safely take birth control pills, tell your doctor if you have any of these other conditions:

• high blood pressure, high cholesterol or triglycerides, or if you are overweight;
• underactive thyroid, diabetes, gallbladder disease;
• seizures or epilepsy; or
• a history of fibrocystic breast disease, lumps, nodules, or an abnormal mammogram.

The hormones in birth control pills can pass into breast milk and may harm a nursing baby. This medication may also slow breast milk production. Do not use if you are breast feeding a baby.

The following serious adverse reactions with the use of COCs are discussed elsewhere in the labeling:

• Serious cardiovascular events and stroke [see BOX WARNING and WARNINGS AND PRECAUTIONS]
• Vascular events [see WARNINGS AND PRECAUTIONS]
• Liver disease [see WARNINGS AND PRECAUTIONS]

Adverse reactions commonly reported by COC users are:

• Irregular uterine bleeding
• Nausea
• Breast tenderness
• Headache

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, the adverse reaction rates observed cannot be directly compared to rates in other clinical trials and may not reflect the rates observed in practice.

Contraception And Folate Supplementation Clinical Trials

The data provided reflect the experience with the use of Yasmin (3 mg DRSP/0.03 mg EE) in the adequate and well-controlled studies for contraception (N=2,837) and folate supplementation (N=172). For contraception, the US pivotal clinical study (N=326) for the oral contraception indication for Yasmin was a multicenter, open-label trial in healthy women aged 18-35 who were treated with Yasmin for up to 13 cycles. The second contraceptive pivotal study (N=442) was a multicenter, randomized, open-label comparative European study of Yasmin vs. 0.150 mg desogestrel/0.03 mg EE conducted in healthy women aged 17-40 who were treated for up to 26 cycles. The primary efficacy study using Safyral for folate supplementation was a randomized, single-center European trial in 172 healthy, female subjects aged 18-40 years comparing the pharmacodynamic effects of Yasmin + 0.451 mg levomefolate calcium to Yasmin co-administered with folic acid during 24 weeks of treatment followed by 20 weeks of open-label Yasmin.

The adverse reactions seen across the 2 indications overlapped and are reported using the frequencies from the pooled dataset. The most common adverse reactions (≥ 2% of users) were: premenstrual syndrome (12.4%), headache/migraine (10.3%), breast pain/tenderness/discomfort (8.1%), nausea/vomiting (4.4%), mood changes (depression, depressed mood, irritability, mood swings, mood altered and affect lability (2.3%), and abdominal pain/discomfort/tenderness (2.2%).

Adverse Reactions (≥ 1%) Leading To Study Discontinuation

Of 2,837 women, 6.7% discontinued from the clinical trials due to an adverse reaction; the most frequent adverse reaction leading to discontinuation was headache/migraine (1.5%).

There were no subjects who discontinued due to an adverse reaction.

Serious Adverse Reactions

Contraception Clinical Trials: depression, pulmonary embolism, toxic skin eruption, and uterine leiomyoma.

Folate Supplementation Clinical Trial: none reported in the clinical trial

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of Yasmin. Because these reactions are 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.

Adverse reactions, including fatalities, are grouped into System Organ Classes and ordered by frequency.

Vascular disorders: Venous and arterial thromboembolic events (including pulmonary emboli, deep vein thrombosis, intracardiac thrombosis, intracranial venous sinus thrombosis, sagittal sinus thrombosis, retinal vein occlusion, myocardial infarction and stroke), hypertension

Hepatobiliary disorders: Gallbladder disease

Immune system disorders: Hypersensitivity

Metabolism and nutrition disorders: Hyperkalemia

Skin and subcutaneous tissue disorders: Chloasma

Read the entire FDA prescribing information for Safyral (Drospirenone/Ethinyl Estradiol/Levomefolate Calcium Tablets and Levomefolate)

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