ZAFEMY: Package Insert and Label Information (Page 5 of 6)

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, and Impairment of Fertility

See Warnings and Precautions (5.3,5.12) and Use in Specific Populations (8.1).

Norelgestromin was tested in in vitro mutagenicity assays (bacterial plate incorporation mutation assay, CHO/HGPRT mutation assay, chromosomal aberration assay using cultured human peripheral lymphocytes) and in one in vivo test (rat micronucleus assay) and found to have no genotoxic potential.

14 CLINICAL STUDIES

In 3 large clinical trials lasting 12 months, in North America, Europe and South Africa, 3,330 women (ages 18 to 45) completed 22,155 cycles of ZAFEMY patch use, the pregnancy rate in women aged 18 to 35 years was 1.07 (95% confidence interval 0.60, 1.76) per 100 woman-years of ZAFEMY patch use. The racial distribution was 91% Caucasian, 4.9% Black, 1.6% Asian, and 2.4% Other.

With respect to weight, 5 of the 15 pregnancies reported with ZAFEMY patch use were among women with a baseline body weight ≥ 198 lbs., which constituted < 3% of the study population. The greater proportion of pregnancies among women at or above 198 lbs. was statistically significant and suggests that ZAFEMY patch may be less effective in these women.

Patch Adhesion

In the clinical trials with ZAFEMY patch, approximately 2% of the cumulative number of patches completely detached and 3% partially detached. The proportion of subjects with at least 1 patch that completely detached ranged from 2% to 6%, with a reduction from Cycle 1 (6%) to Cycle 13 (2%). For instructions on how to manage detachment of patches, refer to Dosage and Administration (2).

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1 How Supplied

ZAFEMY (norelgestromin and ethinyl estradiol transdermal system) is available in one strength of 150 mcg/day NGMN, USP and 35 mcg/day EE, USP.

ZAFEMY is a 12.5 cm2 system with rounded corners with tan backing printed with “Norelgestromin and Ethinyl Estradiol 150/35 mcg per day” in brown ink, protected with a removable translucent oversized dimple slit-release liner. Each patch contains 3.15 mg of norelgestromin, USP and 0.289 mg of ethinyl estradiol, USP.

Each transdermal system is packaged in a protective pouch.

ZAFEMY is available in folding cartons of 1 cycle each (NDC 65162-358-03); each cycle contains 3 systems.

16.2 Special Precautions for Storage and Disposal

Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].

Store patches in their protective pouches. Apply immediately upon removal from the protective pouch.

Do not store in the refrigerator or freezer.

Used patches still contain some active hormones. The sticky sides of the patch should be folded together and the folded patch placed in a sturdy container, preferably with a child-resistant cap, and the container thrown in the trash. Used patches should not be flushed down the toilet.

17 PATIENT COUNSELING INFORMATION

See FDA-approved patient labeling (Patient Information and Instructions for Use)

17.1 General

Counsel patients about the following information:

  • Cigarette smoking increases the risk of serious cardiovascular events from combined hormonal contraceptive use, and that women who are over 35 years old and smoke should not use combined hormonal contraceptives.
  • The use of CHCs increases the risk of VTE. However, pregnancy increases the risk of VTE as much or more than the use of CHCs. The risk of VTE in women using CHCs is 3 to 12 cases per 10,000 woman-years. The risk of VTE is highest during the first year of use of CHCs and when restarting hormonal contraception after a break of 4 weeks or longer. The risk of thromboembolic disease due to CHCs gradually disappears after use is discontinued.
  • ZAFEMY does not protect against HIV infection (AIDS) and other sexually transmitted infections.
  • The Warnings and Precautions associated with combined hormonal contraceptives.
  • ZAFEMY is not to be used during pregnancy; if pregnancy occurs during use of ZAFEMY, instruct the patient to stop further use.
  • Apply a single patch the same day every week (Weeks 1 through 3). Instruct patients what to do in the event a patch is missed. See “WHAT IF I FORGET TO CHANGE MY PATCH?” section in FDA-Approved Patient Labeling.
  • Use a back-up or alternative method of contraception when enzyme inducers are used with ZAFEMY.
  • Combined hormonal contraceptives may reduce breast milk production; this is less likely to occur if breastfeeding is well established.
  • Women who start combined hormonal contraceptives postpartum, and who have not yet had a period, should use an additional method of contraception until they have used a patch for 7 consecutive days.
  • Amenorrhea may occur. Consider pregnancy in the event of amenorrhea. Rule out pregnancy in the event of amenorrhea in two or more consecutive cycles, amenorrhea in one cycle if the woman has not adhered to the dosing schedule, or if associated with symptoms of pregnancy, such as morning sickness or unusual breast tenderness.
  • If the ZAFEMY patch becomes partially or completely detached and remains detached, insufficient drug delivery occurs.
  • A patch should not be re-applied if it is no longer sticky, becomes stuck to itself or another surface, has other material stuck to it, or has become loose or fallen off before. If a patch cannot be re-applied, a new patch should be applied immediately. Supplemental adhesives or wraps should not be used.
  • A woman may not be protected from pregnancy if a patch is partially or completely detached for ≥24 hours (or if the woman is not sure how long the patch has been detached). She should start a new cycle immediately by applying a new patch. Back-up contraception, such as a condom and spermicide or diaphragm and spermicide, must be used for the first week of the new cycle.

All trademarks are the property of their respective owners.

Distributed by:
Amneal Pharmaceuticals LLC
Bridgewater, NJ 08807

Rev. 04-2022-04

Patient Information

ZAFEMY ® (za fe ʹ my) (norelgestromin and ethinyl estradiol transdermal system)

What is the most important information I should know about ZAFEMY?

Do not use ZAFEMY if you smoke cigarettes and are over 35 years old. Smoking increases your risk of serious cardiovascular side effects from hormonal birth control methods, including death from heart attack, blood clots or stroke. This risk increases with age and the number of cigarettes you smoke.

Do not use ZAFEMY if you have an increased risk for blood clots.

Do not use ZAFEMY if your Body Mass Index (BMI) is 30 kg/m2 or more. Women with a BMI of 30 kg/m2 or more who use ZAFEMY may be at a higher risk for developing blood clots compared to women with a BMI lower than 30 kg/m2.

Hormonal birth control methods help to lower the chances of becoming pregnant. They do not protect against HIV infection (AIDS) and other sexually transmitted infections.

What is ZAFEMY?

ZAFEMY is a birth control patch for women with a BMI less than 30 kg/m2. It contains two female hormones, an estrogen called ethinyl estradiol, and a progestin called norelgestromin.

Hormones from ZAFEMY get into the blood stream and are processed by the body differently than hormones from birth control pills. You will be exposed to about 60% more estrogen if you use ZAFEMY than if you use a typical birth control pill containing 35 micrograms of estrogen. In general, increased estrogen may increase the risk of side effects.

How well does ZAFEMY work?

Your chance of getting pregnant depends on how well you follow the directions for using ZAFEMY. The better you follow the directions, the less chance you have of getting pregnant.

In clinical studies, 1 to 2 out of 100 women got pregnant during the first year that they used ZAFEMY.

ZAFEMY may not be as effective in women weighing more than 198 lbs. (90 kg). If you weigh more than 198 lbs. (90 kg), talk to your healthcare provider about which method of birth control is right for you.

The following chart shows the chance of getting pregnant for women who use different methods of birth control. Each box on the chart contains a list of birth control methods that are similar in effectiveness. The most effective methods are at the top of the chart. The box on the bottom of the chart shows the chance of getting pregnant for women who do not use birth control and are trying to get pregnant.

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Do not use ZAFEMY if you:

  • smoke and are over 35 years old
  • have or have had blood clots in your arms, legs, eyes or lungs
  • have an inherited problem that makes your blood clot more than normal
  • have had a stroke
  • have had a heart attack
  • have certain heart valve problems or heart rhythm problems that can cause blood clots to form in the heart
  • have high blood pressure that medicine cannot control
  • have diabetes with kidney, eye, nerve, or blood vessel damage
  • have had certain kinds of severe migraine headaches with aura, numbness, weakness or changes in vision, or have any migraine headaches if you are over age 35
  • have a BMI of 30 or more
  • have liver disease, including liver tumors, take any Hepatitis C drug combination containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir. This may increase levels of the liver enzyme “alanine aminotransferase” (ALT) in the blood.
  • have unexplained vaginal bleeding
  • are pregnant or think you may be pregnant. However, ZAFEMY is not known to cause birth defects when used by accident during pregnancy.
  • have had breast cancer or any cancer that is sensitive to female hormones

Hormonal birth control methods may not be a good choice for you if you have ever had jaundice (yellowing of the skin or eyes) caused by pregnancy or related to previous use of hormonal birth control.

Tell your healthcare provider if you have ever had any of the above conditions. Your healthcare provider may recommend another method of birth control.

Before you use ZAFEMY, tell your healthcare provider:

  • about all your medical conditions
  • if you are pregnant or think you are pregnant
  • if you are scheduled for surgery. ZAFEMY may increase your risk of blood clots after surgery. You should stop using your ZAFEMY patch at least 4 weeks before you have surgery and not restart it until at least 2 weeks after your surgery.
  • if you are scheduled for any laboratory tests. Certain blood tests may be affected by hormonal birth control methods.
  • are breastfeeding or plan to breastfeed. Hormonal birth control methods that contain estrogen, like ZAFEMY, may decrease the amount of milk you make. A small amount of hormones from the ZAFEMY patch may pass into your breast milk. Consider another method of birth control until you are ready to stop breastfeeding.

Tell your healthcare provider about all medicines and herbal products that you take.

Some medicines and herbal products may make hormonal birth control less effective, including, but not limited to:

  • certain seizure medicines (carbamazepine, felbamate, oxcarbazepine, phenytoin, rufinamide, and topiramate)
  • aprepitant
  • barbiturates
  • bosentan
  • griseofulvin
  • certain combinations of HIV medicines (nelfinavir, ritonavir, ritonavir-boosted protease inhibitors)
  • certain non-nucleoside reverse transcriptase inhibitors (nevirapine)
  • rifampin and rifabutin
  • St. John’s wort

Use another birth control method (such as a condom and spermicide or diaphragm and spermicide) when you take medicines that may make the ZAFEMY patch less effective.

Some medicines and grapefruit juice may increase your level of the hormone ethinyl estradiol if used together, including:

  • acetaminophen
  • ascorbic acid
  • medicines that affect how your liver breaks down other medicines (itraconazole, ketoconazole, voriconazole, and fluconazole)
  • certain HIV medicines (atazanavir, indinavir)
  • atorvastatin
  • rosuvastatin
  • etravirine

Hormonal birth control methods may interact with lamotrigine, an anti-seizure medicine used for epilepsy. This may increase the risk of seizures, so your healthcare provider may need to adjust the dose of lamotrigine.

Women on thyroid replacement therapy may need increased doses of thyroid hormone.

Know the medicines you take. Keep a list of them to show your doctor and pharmacist when you get a new medicine.

How should I use ZAFEMY?

  • For detailed instructions, see the step-by-step instructions for using ZAFEMY at the end of this Patient Information.
  • Use ZAFEMY exactly as your healthcare provider tells you to use it.
  • Wear 1 ZAFEMY patch at a time. Make sure you remove your old ZAFEMY patch before applying your new ZAFEMY patch.
  • Do not skip using any ZAFEMY patches, even if you do not have sex often.
  • ZAFEMY is applied in a 4-week cycle.
  • Apply your ZAFEMY patch 1 time each week for 3 weeks (21 total days).
  • Apply each new ZAFEMY patch on the same day of the week. This day will be your “Patch Change Day.” For example, if you apply your first ZAFEMY patch on a Monday, all of your ZAFEMY patches should be applied on a Monday.
  • Do not apply your ZAFEMY patch during Week 4. Make sure you remove your old ZAFEMY patch. This is your patch-free week. Your menstrual period should start during your patch-free week.
  • Begin a new 4 week cycle by applying a new ZAFEMY patch on the day after Week 4 ends. Repeat the cycle of 3 weekly applications followed by a patch-free week.
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  • Your ZAFEMY patch should never be off for more than 7 days in a row. If your ZAFEMY patch is off for more than 7 days in a row and you have sex during this time, you could become pregnant.
  • If you miss a period you might be pregnant. Some women miss their periods or have light periods on hormonal birth control methods even when they are not pregnant. Call your healthcare provider if you miss 1 period and have not used your ZAFEMY patch every day or you miss 2 periods in a row.

What are the possible side effects of ZAFEMY?

See “What is the most important information I should know about ZAFEMY?”

ZAFEMY may cause serious side effects, including:

  • blood clots. Like pregnancy, hormonal birth control methods increase the risk of serious blood clots (see following graph), especially in women who have other risk factors, such as smoking, high blood pressure, high levels of fat in the blood, diabetes, obesity, a family history of blood clots, or age greater than 35. This increased risk is highest when you first start using hormonal birth control and when you restart the same or different hormonal birth control after not using it for a month or more. Some studies have reported that women who use ZAFEMY have a higher risk of getting a blood clot. Talk with your healthcare provider about your risk of getting a blood clot before using ZAFEMY or deciding which type of birth control is right for you.

It is possible to die or be permanently disabled from a problem caused by a blood clot, such as a heart attack or a stroke. Some examples of serious blood clots are blood clots in the:

  • legs (deep vein thrombosis)
  • lungs (pulmonary embolus)
  • eyes (loss of eyesight)
  • heart (heart attack)
  • brain (stroke)

To put the risk of developing a blood clot into perspective: If 10,000 women who are not pregnant and do not use hormonal birth control are followed for one year, between 1 and 5 of these women will develop a blood clot. The figure below shows the likelihood of developing a serious blood clot for women who are not pregnant and do not use hormonal birth control, for women who use hormonal birth control, for pregnant women, and for women in the first 12 weeks after delivering a baby.

Likelihood of Developing a Serious Blood Clot (Venous Thromboembolism [VTE])

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*CHC=combination hormonal contraception

**Pregnancy data based on actual duration of pregnancy in the reference studies. Based on a model assumption that pregnancy duration is nine months, the rate is 7 to 27 per 10,000 WY.

Call your healthcare provider right away if you have:

  • leg pain that will not go away
  • sudden shortness of breath
  • sudden blindness, partial or complete
  • severe pain or pressure in your chest
  • sudden, severe headache unlike your usual headaches
  • weakness or numbness in an arm or leg, or trouble speaking
  • yellowing of the skin or eyeballs

Other serious risks include

  • liver problems including liver tumors
  • gallbladder disease
  • high blood pressure

The most common side effects of ZAFEMY are:

  • breast symptoms (discomfort, swelling, or pain)
  • nausea
  • headache
  • skin irritation, redness, pain, swelling, itching or rash at the patch application site
  • stomach pain
  • pain during menstruation
  • vaginal bleeding and menstrual disorders, such as spotting or bleeding between periods
  • mood, affect and anxiety disorders

Some women have spotting or light bleeding, breast tenderness, or feel sick to their stomach during ZAFEMY use. If these symptoms occur, do not stop using the ZAFEMY patch. The problem will usually go away. If it doesn’t go away, check with your healthcare provider.

Less common side effects are:

  • acne
  • less sexual desire
  • bloating or fluid retention
  • blotchy darkening of your skin, especially your face
  • high blood sugar, especially in women with diabetes
  • high fat (cholesterol, triglycerides) levels in the blood
  • depression, especially if you have had depression in the past. Call your healthcare provider immediately if you have any thoughts of harming yourself.
  • problems tolerating contact lenses
  • weight gain

Tell your healthcare provider about any side effect that bothers you or that does not go away.

These are not all the possible side effects of ZAFEMY. For more information, ask your healthcare provider or pharmacist.

Call your healthcare provider for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store and throw away used ZAFEMY patches?

  • Store at room temperature between 59°F to 86°F (15°C to 30°C).
  • Do not store ZAFEMY patches outside of their pouches. Apply immediately upon removal from the protective pouch.
  • Do not store in the refrigerator or freezer.
  • Used ZAFEMY patches still contain some active hormones. To throw away the ZAFEMY patch, fold the sticky side of the patch together, place it in a sturdy child-proof container, and place this container in the trash. Do not flush used ZAFEMY patches down the toilet.
  • Return unused, unneeded, or expired patches to your pharmacist.

Keep ZAFEMY and all medicines out of the reach of children.

General information about the safe and effective use of ZAFEMY

Medicines are sometimes prescribed for purposes other than those listed in Patient Information. Do not use ZAFEMY for a condition for which it was not prescribed. Do not give ZAFEMY to other people, even if they have the same symptoms that you have. It may harm them.

You can ask your pharmacist or healthcare provider for information about ZAFEMY that is written for health professionals.

For more information, go to www.amneal.com or call 1-877-835-5472.

What are the ingredients in ZAFEMY?

Active ingredient: norelgestromin, USP and ethinyl estradiol, USP

Inactive ingredient: pigmented polyethylene and polyester backing, polyisobutylene/polybutene adhesive, polybutene, crospovidone, oleyl alcohol, dipropylene glycol, polyethylene terephthalate (PET) film with a silicone coating.

Does hormonal birth control cause cancer?

It is not known if hormonal birth control causes breast cancer. Some studies, but not all, suggest that there could be a slight increase in the risk of breast cancer among current users with longer duration of use.

If you have breast cancer now, or have had it in the past, do not use hormonal birth control because some breast cancers are sensitive to hormones.

Women who use hormonal birth control methods may have a slightly higher chance of getting cervical cancer. However, this may be due to other reasons such as having more sexual partners.

What should I know about my period when using ZAFEMY?

When you use ZAFEMY you may have bleeding and spotting between periods, called unplanned bleeding. Unplanned bleeding may vary from slight staining between menstrual periods to breakthrough bleeding which is a flow much like a regular period. Unplanned bleeding occurs most often during the first few months of ZAFEMY use, but may also occur after you have been using the patch for some time. Such bleeding may be temporary and usually does not indicate any serious problems. It is important to continue using the patch on schedule. If the unplanned bleeding or spotting is heavy or lasts for more than a few days, you should discuss this with your healthcare provider.

What if I miss my scheduled period when using ZAFEMY?

Some women miss periods on hormonal birth control, even when they are not pregnant. However, if you go 2 or more months in a row without a period, or you miss your period after a month where you did not use all of your patches correctly, or you have symptoms associated with pregnancy, such as morning sickness or unusual breast tenderness, call your healthcare provider because you may be pregnant. Stop taking ZAFEMY if you are pregnant.

What if I want to become pregnant?

You may stop using ZAFEMY whenever you wish. Consider a visit with your healthcare provider for a pre-pregnancy checkup before you stop using the patch.

Distributed by:

Amneal Pharmaceuticals LLC

Bridgewater, NJ 08807Rev. 04-2022-04

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